RESUMO
BACKGROUND AND OBJECTIVE: The biological effects of atmospheric plasma (cold plasma) show its applicability for controlling the etiological factors that involve tissue repair. Thus, the study evaluated the effect of atmospheric plasma therapy in the control of tissue inflammation and bone remodeling in experimental periodontitis. METHODS: Fifty-six rats were subjected to ligation in the cervical region of the first maxillary molars (8 weeks). The animals were divided into two groups (n = 28): periodontitis without treatment group (P group), and periodontitis with atmospheric plasma treatment group (P + AP group). Tissue samples were collected at 2 and 4 weeks after treatment to analyze the inflammation and bone remodeling by biochemical, histomorphometric, and immunohistochemical analyses. RESULTS: Inflammatory infiltration in the gingival and periodontal ligament was lower in the P + AP group than in the P group (p < .05). The MPO and NAG levels were higher in the P + AP group compared to P group (p < .05). At 4 weeks, the TNF-α level was lower and the IL-10 level was higher in the P + AP group compared to P group (p < .05). In the P + AP group, the IL-1ß level increased in the second week and decreased in the fourth week (p < .05), the number of blood vessels was high in the gingival and periodontal ligament in the second and fourth week (p < .05); and the number of fibroblasts in the gingival tissue was low in the fourth week, and higher in the periodontal tissue in both period (p < .05). Regarding bone remodeling, the RANK and RANKL levels decreased in the P + AP group (p < .05). The OPG level did not differ between the P and P + AP groups (p > .05), but decreased from the second to the fourth experimental week in P + AP group (p < .05). CONCLUSIONS: The treatment of experimental periodontitis with atmospheric plasma for 4 weeks modulated the inflammatory response to favor the repair process and decreased the bone resorption biomarkers, indicating a better control of bone remodeling in periodontal disease.
Assuntos
Remodelação Óssea , Periodontite , Gases em Plasma , Animais , Periodontite/terapia , Periodontite/patologia , Periodontite/sangue , Gases em Plasma/uso terapêutico , Ratos , Masculino , Modelos Animais de Doenças , Inflamação , Gengiva/patologia , Ligamento Periodontal/patologia , Interleucina-1beta/sangue , Interleucina-1beta/análise , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/análise , Interleucina-10/sangue , Interleucina-10/análise , Ligante RANK/análise , Ligante RANK/sangue , Ratos Wistar , Osteoprotegerina/análise , Osteoprotegerina/sangueRESUMO
BACKGROUND AND OBJECTIVE: Periodontitis is an inflammatory disease that destroys periodontal tissues. Interleukin-20 (IL-20), on the other hand, is known as a potent angiogenic, chemotactic, and pro-inflammatory cytokine associated with various chronic inflammatory disorders. IL-20 has a significant role in the regulation of osteoclastogenesis and osteoblastogenesis. This study aimed to evaluate the effect of IL-20 on periodontal destruction. METHODS: In this study, a total of 60 participants were included, 30 of whom were systemically and periodontally healthy (control group), and 30 were systemically healthy but had periodontitis (periodontitis group). Gingival crevicular fluid (GCF) and serum samples were collected from the participants for biochemical analysis. Enzyme-linked immunosorbent assay was used to determine the levels of IL-20, tumor necrosis factor (TNF)-α, IL1ß/IL-10, RANKL/osteoprotegerin (OPG), and matrix metalloproteinase-8 (MMP8). For statistical analysis, the independent t-test, Pearson correlation coefficients, and the Chi-square test were used. RESULTS: GCF IL-20, RANKL, RANKL/OPG, serum IL-20, RANKL, RANKL/OPG, MMP-8, TNF-α, IL-1B, and IL-1ß/IL-10 values were found to be statistically significantly higher in the periodontitis group than in the control group. GCF OPG and serum IL-10 values were found to be statistically significantly higher in the control group than in the periodontitis group. No statistically significant difference was observed between the groups in serum OPG values. A statistically significantly positive correlation was observed between serum IL-20 value and serum RANKL, RANKL/OPG, MMP-8, TNF-α, IL-1ß values, and periodontal clinical parameters. The ROC curves showed: AUC = 0.788 for GCF IL-20, and AUC = 1.000 for serum IL-20. CONCLUSION: According to the results of the study, IL-20 was found to be associated with periodontitis. The role of IL-20 in periodontal pathogenesis is related to osteoclastogenesis and collagen degradation. It is conceivable that IL-20 may increase bone destruction by both affecting the RANKL/OPG ratio and proinflammatory cytokines.
Assuntos
Líquido do Sulco Gengival , Interleucina-1beta , Interleucinas , Metaloproteinase 8 da Matriz , Osteoprotegerina , Periodontite , Ligante RANK , Fator de Necrose Tumoral alfa , Humanos , Interleucinas/sangue , Líquido do Sulco Gengival/química , Masculino , Feminino , Ligante RANK/análise , Ligante RANK/sangue , Adulto , Metaloproteinase 8 da Matriz/sangue , Metaloproteinase 8 da Matriz/análise , Osteoprotegerina/sangue , Osteoprotegerina/análise , Periodontite/metabolismo , Periodontite/sangue , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/análise , Interleucina-1beta/sangue , Interleucina-1beta/análise , Pessoa de Meia-Idade , Interleucina-10/sangue , Interleucina-10/análise , Estudos de Casos e Controles , Ensaio de Imunoadsorção EnzimáticaRESUMO
OBJECTIVE: The aim of this study was to analyze the effects of periodontal treatment on markers of atherosclerotic coronary artery disease and circulating levels of periostin. BACKGROUND: Periostin is necessary for periodontal stability, but it is highly present in atherosclerotic plaques. Treatment of periodontal disease, with low levels of local periostin, is thought to reduce systemic levels of periostin. Thus, this may contribute to cardiovascular health. METHODS: A pilot randomized controlled clinical trial was designed to include patients with severe periodontal disease and history of atherosclerotic coronary artery disease. Samples of gingival crevicular fluid (GCF) and serum were collected before and after periodontal treatment by periodontal surgery or non-surgical therapy. The levels of several markers of inflammation and cardiovascular damage were evaluated including CRP, IFN-γ, IL-1ß, IL-10, MIP-1α, periostin, and TNF-α in GCF and CRP, Fibrinogen, IFN-γ, IL-1ß, IL-6, IL-10, L-Selectin, MIP-1α, Periostin, TNF-α, and vWF in serum. RESULTS: A total of 22 patients with an average of 56 years old were recruited for participating in this study. Twenty of them were male. Most of them (82%) had suffered an acute myocardial event and underwent surgery for placing 1, 2, or 3 stents in the coronary arteries more than 6 months ago but less than 1 year. The treatment of periodontal disease resulted in an overall improvement of all periodontal parameters. Regarding the evaluation of GCF and serum, a significant increase of periostin in the GCF was observed after periodontal surgery. In contrast, although other markers in GCF and serum improved, no significant correlations were found. CONCLUSION: Treatment of periodontal disease through periodontal surgery induces a local and transient increase in the levels of periostin in the gingival crevicular fluid. The effects on systemic markers of inflammation and cardiovascular function have not been confirmed.
Assuntos
Biomarcadores , Moléculas de Adesão Celular , Doença da Artéria Coronariana , Líquido do Sulco Gengival , Doenças Periodontais , Humanos , Masculino , Projetos Piloto , Pessoa de Meia-Idade , Feminino , Moléculas de Adesão Celular/análise , Moléculas de Adesão Celular/sangue , Moléculas de Adesão Celular/metabolismo , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Líquido do Sulco Gengival/química , Líquido do Sulco Gengival/metabolismo , Biomarcadores/análise , Biomarcadores/sangue , Doenças Periodontais/metabolismo , Doenças Periodontais/complicações , Interleucina-10/análise , Interleucina-10/sangue , Proteína C-Reativa/análise , Interferon gama/análise , Interferon gama/sangue , Idoso , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , PeriostinaRESUMO
BACKGROUND: Cystic fibrosis (CF) is a genetic multisystem disorder. Inflammatory processes, which presumably begin early in infancy, play a crucial role in the progression of the disease. The detection of inflammatory biomarkers, especially in the airways, has therefore gained increasing attention. Due to improved treatment options, patients with CF produce less sputum. Nasal lavage samples therefore represent a promising alternative to induced sputum or bronchoalveolar lavage specimens. However, methodology of cytokine measurements is not standardised and comparisons of results are therefore often difficult. The aim of this study was to identify suitable detection methods of cytokines in nasal lavage samples by comparison of two different assays. METHODS: Nasal lavage samples were obtained from the same patient at the same time by trained respiratory physiotherapists using a disposable syringe and 10 ml of 0.9% sodium chloride per nostril during outpatient visits. The cytokines IL-17 A, IL-2, IL-6 and IL-10 were measured using two different assays (BD™ and Milliplex®), which have already been applied in sputum and nasal lavage samples, despite different lower detection limits. RESULTS: 22 participants were included in the study. In 95.5% of measurements, values were below the limit of detection with respect to the BD™ assay. Only IL-6 could be detected in approximately half of the patients. Individual cytokine levels were considerably higher when measured with Milliplex®, which is also reflected in a statistically significant manner (p = < 0.01). CONCLUSION: The right choice of analysis method is crucial for measuring inflammatory markers in nasal lavage samples. Compared to the literature, Milliplex® showed higher detection rates and similar concentrations to other studies. TRIAL REGISTRATION: Ethics approval was obtained from the ethics committee at Medical University of Innsbruck (EK Nr: 1055/2022).
Assuntos
Fibrose Cística , Citocinas , Líquido da Lavagem Nasal , Humanos , Fibrose Cística/diagnóstico , Masculino , Feminino , Citocinas/análise , Citocinas/metabolismo , Adulto , Adolescente , Líquido da Lavagem Nasal/química , Adulto Jovem , Biomarcadores/análise , Biomarcadores/metabolismo , Criança , Interleucina-6/análise , Interleucina-6/metabolismo , Interleucina-10/análise , Interleucina-10/metabolismo , Interleucina-2/análise , Interleucina-2/metabolismo , Interleucina-17/análise , Interleucina-17/metabolismoRESUMO
BACKGROUND: The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth. METHODS: On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software. RESULTS: A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01). CONCLUSIONS: The inflammatory biomarkers IL-1ß, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.
The premature foetus has many serious complications in the near and long term because of the immature organs, which is related to the long-term incidence of cerebral palsy, developmental delay and retinopathy of prematurity, which is the main cause of perinatal foetal death. Preterm birth cases are accompanied by infection of pathogenic microorganisms in amniotic cavity, which then leads to inflammatory reaction in amniotic cavity. However, research on the correlation between inflammatory markers and preterm birth has shown certain complexity and differences. The results of this meta-analysis show that the inflammatory biomarkers interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and interleukin-10 (IL-10), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in amniotic fluid of patients in the second- or third-trimester pregnancy are significant between the preterm birth group and the control group, and the expression level of inflammatory factors in amniotic fluid of patients in the preterm birth group is elevated, thus suggesting that these inflammatory factors may be able to predict preterm birth.
Assuntos
Líquido Amniótico , Biomarcadores , Nascimento Prematuro , Feminino , Humanos , Gravidez , Líquido Amniótico/química , Líquido Amniótico/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Inflamação/metabolismo , Interleucina-10/análise , Interleucina-10/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/metabolismo , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Nascimento Prematuro/metabolismoRESUMO
Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods: We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild (n = 7), moderate (n = 19), or severe (n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Results: The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group (p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.005 and p < 0.0001, respectively). Conclusions: In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.
Assuntos
Inflamação , Interleucina-10 , Fígado , Obesidade Mórbida , Humanos , Interleucina-10/sangue , Interleucina-10/análise , Obesidade Mórbida/complicações , Obesidade Mórbida/sangue , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Fígado/metabolismo , Fígado/patologia , Estudos Prospectivos , Inflamação/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicaçõesRESUMO
Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is continuously targeting people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to analyze specific biomarkers, namely ACRP-30, IL-10, TNF-α, and IL-6, in knee synovial fluid, and correlate them with KOA patients' clinical data, radiographic changes, and functional and pain scores. Materials and Methods: 24 subjects with KOA and over 50 years of age participate in the present study. Synovial fluid was harvested using ultrasound guidance from the target knees of the enrolled KOA patients, and the levels of ACRP-30, IL-10, TNF-α, and IL-6 were measured using enzyme-linked immunosorbent assays (ELISA). All patients underwent a supine X-ray at the target knee and were classified using Kellgren-Lawrence (K-L) grading. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p = 0.0451, r = -0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p = 0.0405, r = -0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p = 0.0079, r = 0.7993), compared to women (p = 0.0203, r = 0.6223). In the case of women, the progression of the disease tends to increase more intensively the WOMAC score's total values (p = 0.00031, r = 0.8342), compared with men (p = 0.0289, r = 7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI; in addition, women seem to be more sensitive to pain and stiffness.
Assuntos
Adiponectina , Biomarcadores , Citocinas , Interleucina-10 , Osteoartrite do Joelho , Fator de Necrose Tumoral alfa , Humanos , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Adiponectina/sangue , Adiponectina/análise , Idoso , Citocinas/sangue , Citocinas/análise , Biomarcadores/análise , Biomarcadores/sangue , Interleucina-10/sangue , Interleucina-10/análise , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangue , Interleucina-6/sangue , Interleucina-6/análise , Líquido Sinovial/química , Líquido Sinovial/metabolismo , Ensaio de Imunoadsorção EnzimáticaRESUMO
Background/aim: Laser biostimulation therapy (LBT) is suggested to have positive effects on periodontal healing. This study evaluated LBT with nonsurgical periodontal therapy (NSPT) in diabetes mellitus (DM) and systemic health (SH) conditions. Materials and methods: Thirty periodontitis patients (15 with DM and 15 with SH) were included in the study, which had a split-mouth design, by applying LBT in the mouth of the same systemic condition. Thus, 4 study groups were formed, as 1) NSPT - DM: NSPT alone in DM, 2) NSPT + LBT - DM: NSPT + LBT application in DM, 3) NSPT - SH: NSPT alone in SH, and 4) NSPT + LBT - SH: NSPT + LBT application in SH. NSPT was performed on days 15, 30, 37, 44, 51, 58, and 65. LBT was performed 6 times on days 30, 37, 44, 51, 58, and 65 with an Nd:YAG laser. The plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were assessed as the clinical parameters and recorded at baseline and days 30, 37, and 72. Gingival crevicular fluid levels of interleukin 1 beta (IL-1ß) and IL-10 were evaluated by ELISA as the biochemical parameters at baseline and on days 30, 37, and 72. Results: Clinical parameters had improved in all of the groups on day 72 (p < 0.01). PPD and CAL improved more in the DM group with NSPT and LBT group than in the DM group with NSPT without LBT on day 37 (p < 0.05). IL-1ß decreased and IL-10 increased in all of the groups on day 72 (p < 0.01). This change was more evident in the DM group with NSPT and LBT than in the DM group with NSPT without LBT on day 7 (p < 0.05). Conclusion: These results revealed the short-term impacts of LBT on periodontal healing, which return to ineffectiveness with repeated irradiation. Therefore, it may be speculated that LBT via the protocol herein may have a short-term antiinflammatory contribution to NSPT, only in impaired healing conditions such as DM.
Assuntos
Periodontite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos de Casos e Controles , Periodontite/terapia , Líquido do Sulco Gengival/química , Índice Periodontal , Terapia com Luz de Baixa Intensidade/métodos , Interleucina-1beta/metabolismo , Interleucina-1beta/análise , Terapia a Laser/métodos , Interleucina-10/metabolismo , Interleucina-10/análiseRESUMO
Background and Objectives: An obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and to examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis-resistant obese individuals. Materials and Methods: Thirty-nine participants in good periodontal health were recruited. Twenty patients were classified as lean and nineteen as obese based on their BMI levels. A thorough periodontal assessment was carried out. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were analyzed for interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A), and CRP. Results: GCF CRP levels were significantly higher in the obese than in the lean individuals. No statistically significant differences were noted between the two groups in either GCF or blood in terms of any of the inflammatory cytokine levels. IL-17A was not detected in the GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, and the association tended to be stronger in the obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels were positively associated with multiple GCF inflammatory cytokines (e.g., IL-1ß, IL-6, IL-8, and TNF-α) in all subjects, the associations tended to be weaker in the obese individuals (e.g., IL-1ß, IL-6, and TNF-α). Furthermore, the levels of the GCF inflammatory cytokines IL-6 and TNF-α were decreased in the obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a weakened inflammatory cytokine response in the gingival tissues of obese individuals.
Assuntos
Citocinas , Interleucina-8 , Humanos , Citocinas/metabolismo , Interleucina-8/análise , Interleucina-10/análise , Interleucina-6/análise , Fator de Necrose Tumoral alfa/análise , Proteína C-Reativa/análise , Interleucina-1beta/análise , Líquido do Sulco Gengival/química , Líquido do Sulco Gengival/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Inflamação/complicações , Inflamação/metabolismoRESUMO
BACKGROUND: Regulatory T cells are known to play a key role to counter balance the protective immune response and immune mediated pathology. However, the role of naturally occurring regulatory cells CD4+CD25+Foxp3+ in malaria infection during the disease pathogenesis is controversial. Beside this, ICOS molecule has been shown to be involved in the development and function of regulatory T cell enhance IL-10 production. Therefore, possible involvement of the ICOS dependent regulatory CD4+ICOS+Foxp3+ T cells in resistance/susceptibility during malaria parasite is explored in this study. METHODS: 5 × 105 red blood cells infected with non-lethal and lethal parasites were inoculated in female Balb/c mice by intra-peritoneal injection. Infected or uninfected mice were sacrificed at early (3rd day post infection) and later stage (10th day post infection) of infection. Harvested cells were analysed by using flow cytometer and serum cytokine by Bioplex assay. RESULTS: Thin blood films show that percentages of parasitaemia increases with disease progression in infections with the lethal malaria parasite and mice eventually die by day 14th post-infection. Whereas in case of non-lethal malaria parasite, parasitaemia goes down by 7th day post infection and gets cleared within 13th day. The number of CD4+ ICOS+ T cells increases in lethal infection with disease progression. Surprisingly, in non-lethal parasite, ICOS expression decreases after day 7th post infection as parasitaemia goes down. The frequency of CD4+ICOS+FoxP3+ Tregs was significantly higher in lethal parasitic infection as compared to the non-lethal parasite. The level of IL-12 cytokine was remarkably higher in non-lethal infection compared to the lethal infection. In contrast, the level of IL-10 cytokines was higher in lethal parasite infection compared to the non-lethal parasite. CONCLUSION: Taken together, these data suggest that lethal parasite induce immunosuppressive environment, protecting from host immune responses and help the parasite to survive whereas non-lethal parasite leads to low frequencies of Treg cells seldom impede immune response that allow the parasite to get self-resolved.
Assuntos
Malária/etiologia , Linfócitos T Reguladores/fisiologia , Animais , Antígenos CD4/fisiologia , Citocinas/análise , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/fisiologia , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis/fisiologia , Interleucina-10/análise , Malária/diagnóstico , Malária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Parasitemia/diagnóstico , Parasitemia/parasitologia , Fragmentos de Peptídeos/fisiologia , Plasmodium berghei , Plasmodium chabaudi , Plasmodium yoelii , Organismos Livres de Patógenos Específicos , Baço/citologiaRESUMO
BACKGROUND: Since the first observations of patients with COVID-19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet. OBJECTIVE: We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial-endothelial barrier. METHODS: One hundred seventy-four COVID-19 patients with respiratory symptoms, 92 admitted to the intermediate medicine ward (IMW) and 82 to the intensive care unit (ICU) at Luigi Sacco Hospital in Milan, were studied. RESULTS: Baseline characteristics at admission were considered. Proteins, interleukin 8 (IL-8) and interleukin 10 (IL-10) in bronchoalveolar lavage fluid (BALF) were analysed in 26 ICU patients. In addition, ten autopsy ultrastructural lung studies were performed in patients with COVID-19 and compared with postmortem findings in a control group (bacterial pneumonia-ARDS and H1N1-ARDS). ICU patients had lower serum albumin than IMW patients [20 (18-23) vs 28 (24-33) g L-1 , P < 0.001]. Serum albumin was lower in more compromised groups (lower PaO2 -to-FiO2 ratio and worst chest X-ray findings) and was associated with 30 days of probability of survival. Protein concentration was correlated with IL-8 and IL-10 levels in BALF. Electron microscopy examinations of eight out of ten COVID-19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells. CONCLUSION: Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID-19 and might be a potential therapeutic target.
Assuntos
COVID-19/complicações , Hipoalbuminemia/etiologia , Idoso , Líquido da Lavagem Broncoalveolar/química , COVID-19/sangue , Síndrome de Vazamento Capilar/etiologia , Endotélio Vascular/patologia , Feminino , Humanos , Interleucina-10/análise , Interleucina-8/análise , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Respiratória/patologia , Estudos Retrospectivos , UltrassonografiaRESUMO
Advanced cystic fibrosis (CF) lung disease is commonly characterized by a chronic Pseudomonas aeruginosa infection and destructive inflammation caused by neutrophils. However, the lack of convincing evidence from most informative biomarkers of severe lung dysfunction (SLD-CF) has hampered the formulation of a conclusive, targeted diagnosis of CF. The aim of this study was to determine whether SLD-CF is related to the high concentration of sputum inflammatory mediators and the presence of biofilm-forming bacterial strains. Forty-one patients with advanced CF lung disease were studied. The severity of pulmonary dysfunction was defined by forced expiratory volume in 1 second (FEV1) < 40%. C-reactive protein (CRP) and NLR (neutrophil-lymphocyte ratio) were examined as representative blood-based markers of inflammation. Expectorated sputum was collected and analysed for cytokines and neutrophil-derived defence proteins. Isolated sputum bacteria were identified and their biofilm-forming capacity was determined. There was no association between FEV1% and total number of sputum bacteria. However, in the high biofilm-forming group the median FEV1 was < 40%. Importantly, high density of sputum bacteria was associated with increased concentrations of neutrophil elastase and interleukin (IL)-8 and low concentrations of IL-6 and IL-10. The low concentration of sputum IL-6 is unique for CF and distinct from that observed in other chronic pulmonary inflammatory diseases. These findings strongly suggest that expectorated sputum is an informative source of pulmonary biomarkers representative for advanced CF and may replace more invasive bronchoalveolar lavage analysis to monitor the disease. We recommend to use of the following inflammatory biomarkers: blood CRP, NLR and sputum elastase, IL-6, IL-8 and IL-10.
Assuntos
Fibrose Cística/patologia , Interleucina-6/análise , Interleucina-8/análise , Elastase de Leucócito/análise , Infecções Respiratórias/patologia , Escarro/química , Adolescente , Adulto , Biofilmes/crescimento & desenvolvimento , Biomarcadores/análise , Proteína C-Reativa/análise , Criança , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Mediadores da Inflamação/análise , Interleucina-10/análise , Contagem de Linfócitos , Masculino , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/imunologia , Infecções Respiratórias/microbiologia , Escarro/imunologia , Escarro/microbiologia , Adulto JovemRESUMO
There is a lack of evidence on the effects of high-intensity interval training (HIIT) microcycle duration on the antioxidant capacity and hippocampal inflammatory response of young (immature) samples. This study compared two HIIT microcycles lengths on adaptation to training, antioxidant balance, and systemic and hippocampal inflammation in immature rats. Twenty-four immature Wistar rats (27 days) were equally divided into groups: control; 4-day HIIT (3 training days + 1 rest day); and 7-day HIIT (6 training days + 1 rest day). Both microcycles of 4 and 7 days were 28 days of training (37-38 m min-1). Running performance improved in all training groups compared to controls (P < 0.05). However, the 7-day HIIT group statistically increased serum interleukin-6 (IL-6) compared to the control and 4-day HIIT groups (P < 0.05). The total serum antioxidant capacity in the 7-day HIIT group was statistically lower than in the control group (P < 0.05). There was no statistical difference for the analysis of serum malondialdehyde between the groups. The hippocampal gene expression of IL-6, IL-1ß, IL-10, and tumor necrosis factor-alpha in the training groups was statistically higher than in the control group (P = 0.01), with no significant difference between the 4-day HIIT and 7-day HIIT groups. We concluded that HIIT microcycles with a longer duration decrease the antioxidant capacity and increase the systematic and hippocampal inflammation. Thus, we suggest using short HIIT microcycles for young (immature) groups due to improved running performance with less inflammatory and antioxidant changes.
Assuntos
Treinamento Intervalado de Alta Intensidade/métodos , Atividade Motora/fisiologia , Adaptação Fisiológica , Animais , Antioxidantes/metabolismo , Hipocampo/imunologia , Inflamação/metabolismo , Interleucina-10/análise , Interleucina-1beta/análise , Interleucina-6/análise , Interleucina-6/sangue , Masculino , Malondialdeído , Condicionamento Físico Animal/métodos , Ratos , Ratos Wistar , Fatores de Tempo , Fator de Necrose Tumoral alfa/análiseRESUMO
BACKGROUND: The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance. METHODS: This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1ß, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations. RESULTS: Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1ß, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period. CONCLUSION: EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal. TRIAL REGISTRATION: NCT03231748, registered on 27th July 2017.
Assuntos
Injúria Renal Aguda/etiologia , Citocinas/metabolismo , Taxa de Depuração Metabólica/fisiologia , Sepse/complicações , Injúria Renal Aguda/fisiopatologia , Idoso , Quimiocina CCL2/análise , Quimiocina CCL2/sangue , Fator de Crescimento Epidérmico/análise , Fator de Crescimento Epidérmico/sangue , Feminino , Humanos , Interferon gama/análise , Interferon gama/sangue , Interleucina-10/análise , Interleucina-10/sangue , Interleucina-1alfa/análise , Interleucina-1alfa/sangue , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-2/análise , Interleucina-2/sangue , Interleucina-4/análise , Interleucina-4/sangue , Interleucina-6/análise , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Terapia de Substituição Renal/métodos , Sepse/fisiopatologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangue , Fatores de Crescimento do Endotélio Vascular/análise , Fatores de Crescimento do Endotélio Vascular/sangueRESUMO
BACKGROUND: Persistent allergic airway diseases cause a great burden worldwide. Their pathogenesis is not clear enough. There is evidence that one of the recently described cytokine interleukin (IL) 22 may be involved in the pathogenesis of these diseases. Scientists argue if this cytokine acts as proinflammatory or anti-inflammatory agent. The aim of this study was to investigate IL-22 level in patients with persistent allergic airway diseases caused by house dust mite (HDM) in comparison with healthy individuals and to evaluate its relationship with IL-13 and IL-10 level, symptoms score and quality of life. METHODS: Patients with persistent allergic rhinitis caused by HDM and having symptoms for at least 2 years with or without allergic asthma were involved into the study. Measurements of IL-22, IL-13 and IL-10 and in serum and nasal lavage was performed by ELISA. Questionnaires assessing symptoms severity and quality of life were used. RESULTS: A tendency was observed that IL-22 in serum and nasal lavage was higher in patients with allergic airway diseases compared to control group (14.86 pg/ml vs. 7.04 pg/ml and 2.67 pg/ml vs. 1.28 pg/ml, respectively). Positive statistically significant correlation was estimated between serum IL-22 and serum IL-10 (rs = 0.57, p < 0.01) and IL-13 (rs = 0.44, p < 0.05) level. Moreover, positive significant correlation was found between IL-22 in nasal lavage and IL-10 in nasal lavage (rs = 0.37, p < 0.05). There was a negative statistically significant correlation between serum IL-22 and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) (rs = - 0.42, p < 0.05). CONCLUSION: Our study showed a possible anti-inflammatory effect of IL-22 in patients with persistent allergic airway diseases caused by HDM.
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Asma/complicações , Interleucinas/análise , Líquido da Lavagem Nasal/química , Pyroglyphidae/imunologia , Rinite Alérgica/imunologia , Adulto , Animais , Anti-Inflamatórios , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-10/análise , Interleucina-13/análise , Masculino , Projetos Piloto , Rinite Alérgica/sangue , Inquéritos e Questionários , Interleucina 22RESUMO
The concentrations of ATP, IL-6, and IL-10 were measured in extracts of plucked hair follicles from healthy volunteers (normal values) and patients with androgenetic alopecia and then, ATP, IL-6, and IL-10 content was calculated for each follicle. The resulting values were directly proportional to hair follicle length, except for IL-6. The concentration of extracted ATP correlated with lactate dehydrogenase activity indicating cell damage. In patients with androgenetic alopecia, IL-10 content exceeded the normal values in follicles with a length <1 mm and ATP content surpassed the normal in follicles >2 mm long. The content of IL-6 and IL-10 measured by ELISA was comparable with results of mRNA expression assayed by RT-PCR, which attested to moderate level of gene expression. The content of ATP and IL- 10, but not IL-6 depended on the length of plucked hair follicle and on pathogenetic factors affecting hair growth.
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Trifosfato de Adenosina/análise , Citocinas/análise , Folículo Piloso/química , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Interleucina-10/análise , Interleucina-6/análise , Masculino , Ratos , Ratos WistarRESUMO
The aim of this study was to evaluate the inflammation process that resulted from the inoculation of Wistar Rats with Acanthamoeba griffini, a virulent T3 Acanthamoeba genotype that produces keratitis. Haematoxylin and eosin, periodic acid stain, immunohistochemistry and morphometry were used to analyse tissues from rats of an Acanthamoeba keratitis (AK) model. Two weeks after inoculating the rats with A griffini trophozoites, the thickness of the stroma had diminished, followed by an increase in thickness at 4 weeks. At the latter time, an abundance of inflammatory infiltrate cells was observed, some found to express IL-1ß, IL-10 and/or caspase 3. Intercellular adhesion molecule-1 was expressed in corneal blood vessels amid the abundant vascularization characteristic of the development of AK. Through an immunohistochemical technique, trophozoites were detected at 2 and 4 weeks post-inoculation. By 8 weeks, there were a low number of trophozoites and cysts and the corneas of infected rats were similar in thickness to those of the controls. Thus, the rats were capable of healing experimental AK in the present rat model. Diverse immunological mechanisms regulated the inflammatory process in acute AK induced by A griffini in a murine model.
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Ceratite por Acanthamoeba/patologia , Acanthamoeba/fisiologia , Acanthamoeba/classificação , Ceratite por Acanthamoeba/imunologia , Animais , Apoptose , Caspase 3/análise , Córnea/patologia , Modelos Animais de Doenças , Feminino , Humanos , Molécula 1 de Adesão Intercelular/análise , Interleucina-10/análise , Interleucina-1beta/análise , Camundongos , Ratos , Ratos Wistar , Trofozoítos/fisiologiaRESUMO
Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.
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Biomarcadores , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/mortalidade , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Pneumonia Viral/mortalidade , Betacoronavirus/patogenicidade , COVID-19 , Coronavirus/patogenicidade , Humanos , Inflamação , Interleucina-10/análise , Interleucina-6/análise , Contagem de Leucócitos/métodos , Contagem de Linfócitos/métodos , Pandemias , Contagem de Plaquetas/métodos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Sepsis is often treated with penicillin-binding protein 3 (PBP-3) acting ß-lactam antibiotics, such as piperacillin-tazobactam, cefotaxime, and meropenem. They cause considerable bacterial structural changes and have in vitro been associated with an increased inflammatory response. In a clinically relevant large animal sepsis model, our primary aim was to investigate whether bacteria killed by a PBP-3-active antibiotic has a greater effect on the early inflammatory response and organ dysfunction compared with corresponding amounts of live or heat-killed bacteria. A secondary aim was to determine whether the addition of an aminoglycoside could mitigate the cefuroxime-induced response. METHOD: Killed or live Escherichia coli were administrated as a 3-h infusion to 16 healthy pigs in a prospective, randomized controlled interventional experimental study. Cefuroxime was chosen as the PBP-3-active antibiotic and tobramycin represented the aminoglycosides. The animals were randomized to receive (I) bacteria killed by cefuroxime, (II) live bacteria, (III) bacteria killed by heat, or (IV) bacteria killed by the combination of cefuroxime and tobramycin. Plasma endotoxin, tumor necrosis factor alpha, interleukin-6, interleukin-10, leukocytes, and organ function were recorded at the start of the experiment and then hourly for 6 h. RESULTS: Differences in dynamics of concentration over time between the four treatment groups were found for the three cytokines (p < 0.001). Animals receiving cefuroxime-killed bacteria demonstrated higher responses than those receiving live (p < 0.05) or heat-killed bacteria (p < 0.01). The addition of tobramycin reduced the cefuroxime-induced responses (p < 0.001). The cytokine responses were associated with leucocyte activation that was further associated with pulmonary dysfunction and increases in lactate (p < 0.01). CONCLUSIONS: In comparison with live or heat-killed bacteria, bacteria killed by a PBP-3-active antibiotic induced an increased inflammatory response that appears to be associated with deteriorated organ and cellular function. The addition of an aminoglycoside to the PBP-3-active antibiotic reduced that response.
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Inflamação/etiologia , Insuficiência de Múltiplos Órgãos/etiologia , Proteínas de Ligação às Penicilinas/efeitos adversos , Sepse/tratamento farmacológico , Animais , Cefuroxima/análise , Cefuroxima/farmacologia , Cefuroxima/uso terapêutico , Modelos Animais de Doenças , Endotoxinas/análise , Endotoxinas/sangue , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/fisiopatologia , Inflamação/complicações , Inflamação/fisiopatologia , Interleucina-10/análise , Interleucina-10/sangue , Interleucina-6/análise , Interleucina-6/sangue , Insuficiência de Múltiplos Órgãos/complicações , Insuficiência de Múltiplos Órgãos/fisiopatologia , Escores de Disfunção Orgânica , Proteínas de Ligação às Penicilinas/uso terapêutico , Estudos Prospectivos , Sepse/fisiopatologia , Suínos , Tobramicina/efeitos adversos , Tobramicina/farmacologia , Tobramicina/uso terapêutico , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Hypertonic sodium lactate (HSL) may be of interest during inflammation. We aimed to evaluate its effects during experimental sepsis in rats (cecal ligation and puncture (CLP)). METHODS: Three groups were analyzed (n = 10/group): sham, CLP-NaCl 0.9%, and CLP-HSL (2.5 mL/kg/h of fluids for 18 h after CLP). Mesenteric microcirculation, echocardiography, cytokines, and biochemical parameters were evaluated. Two additional experiments were performed for capillary leakage (Evans blue, n = 5/group) and cardiac hemodynamics (n = 7/group). RESULTS: HSL improved mesenteric microcirculation (CLP-HSL 736 [407-879] vs. CLP-NaCl 241 [209-391] UI/pixel, p = 0.0006), cardiac output (0.34 [0.28-0.43] vs. 0.14 [0.10-0.18] mL/min/g, p < 0.0001), and left ventricular fractional shortening (55 [46-73] vs. 39 [33-52] %, p = 0.009). HSL also raised dP/dtmax slope (6.3 [3.3-12.1] vs. 2.7 [2.0-3.9] 103 mmHg/s, p = 0.04), lowered left ventricular end-diastolic pressure-volume relation (1.9 [1.1-2.3] vs. 3.0 [2.2-3.7] RVU/mmHg, p = 0.005), and reduced Evans blue diffusion in the gut (37 [31-43] vs. 113 [63-142], p = 0.03), the lung (108 [82-174] vs. 273 [222-445], p = 0.006), and the liver (24 [14-37] vs. 70 [50-89] ng EB/mg, p = 0.04). Lactate and 3-hydroxybutyrate were higher in CLP-HSL (6.03 [3.08-10.30] vs. 3.19 [2.42-5.11] mmol/L, p = 0.04; 400 [174-626] vs. 189 [130-301] µmol/L, p = 0.03). Plasma cytokines were reduced in HSL (IL-1ß, 172 [119-446] vs. 928 [245-1470] pg/mL, p = 0.004; TNFα, 17.9 [12.5-50.3] vs. 53.9 [30.8-85.6] pg/mL, p = 0.005; IL-10, 352 [267-912] vs. 905 [723-1243] pg/mL) as well as plasma VEGF-A (198 [185-250] vs. 261 [250-269] pg/mL, p = 0.009). CONCLUSIONS: Hypertonic sodium lactate fluid protects against cardiac dysfunction, mesenteric microcirculation alteration, and capillary leakage during sepsis and simultaneously reduces inflammation and enhances ketone bodies.