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1.
Orphanet J Rare Dis ; 16(1): 347, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348761

RESUMO

BACKGROUND: Interleukin-10 (IL-10) is an independent factor for predicting adverse outcomes in pediatric patients with hemophagocytic lymphohistiocytosis (HLH). However, little is known about its prognostic value in adult patients. METHODS: This single center retrospective study was conducted to explore the prognostic value of IL-10 in 101 adults newly diagnosed with HLH. The serum interleukin levels were quantitatively determined by chemiluminescence using cytokine profiling kits. RESULTS: Serum IL-10 levels were significantly increased in adult HLH patients. Elevated IL-10 levels was correlated with lower concentrations of hemoglobin (r = - 0.279, P = 0.005). IL-10 levels were significantly lower in patients with macrophage activation syndrome (MAS) than in those with infection-associated HLH (IAHS) and malignancy-associated HLH (MAHS) (P = 0.033, P = 0.012). Patients with MAS had relatively longer survival than those with IAHS and MAHS (P < 0.001). Univariate analysis indicated that hemoglobin < 8.2 g/dL, platelets < 40 × 109/L, lactate dehydrogenase ≥ 700 IU/L, albumin < 28 g/L, post-treatment ferritin > 1050 µg/L and IL-10 ≥ 129 pg/mL were poor prognostic factors for survival. However, multivariate analysis revealed that only high serum IL-10 levels (≥ 129 pg/mL) at diagnosis and high post-treatment ferritin levels (> 1050 µg/L) were independent risk factors for poor overall survival in adult HLH patients (HR: 4.087, 95% CI 2.064-8.090, P < 0.001; HR 3.814, 95% CI 2.042-7.126, P < 0.001, respectively). CONCLUSIONS: Our results suggest that higher serum IL-10 levels might be a prognostic marker in adult HLH patients.


Assuntos
Interleucina-10/sangue , Linfo-Histiocitose Hemofagocítica , Adulto , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Prognóstico , Estudos Retrospectivos
2.
Front Immunol ; 12: 653611, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290697

RESUMO

Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints. Single-nucleotide polymorphisms (SNPs) in genes encoding cytokines have been associated with AS, which can interfere with the production of these cytokines and contribute to the development of AS. In order to contribute to a better understanding of the pathology of AS, our objective was to investigate a possible association of the IL10 -1082 A>G SNP (rs1800896) with AS and to evaluate the serum levels of TNF-α, IL-10, IL-17A, and IL-17F in AS patients and controls comparing them with their respective genotypes (TNF rs1800629, IL10 rs1800896, IL17A rs2275913, and IL17F rs763780). Patients and controls were selected from the Maringá University Hospital and the Maringá Rheumatism Clinic, in Paraná State, Southern Brazil, and they were diagnosed by the ASAS Criteria. In total, 149 patients and 169 controls were genotyped for the IL10 -1082 A>G polymorphism using a polymerase chain reaction with sequence specific primers (PCR-SSP); the measurement of TNF-α serum levels was performed through the immunofluorimetric test and IL-10, IL-17A, and IL-17F using an ELISA test. There was a high frequency of the IL10 -1082 G allele in AS patients compared with controls with an odds ratio of 1.83 and 95% confidence interval of 1.32 to 2.54, and a significant difference in the genotype frequencies of the IL10 -1082 A/G+G/G between patients and healthy controls, with an odds ratio of 3.01 and 95% confidence interval of 1.75 to 5.17. In addition, increased serum levels of IL-10 were observed in AS patients: 2.38 (IQR, 0.91) pg/ml compared with controls 1.72 (IQR 0.93) pg/ml (P = 0.01). Our results also showed an association between IL17F rs763780 C/T+T/T genotypes and increased serum levels of IL-17F in patients with AS and also in controls. We can conclude that patients with the A/G and G/G genotypes for -1082 A>G (rs1800896) in the IL10 gene are three times more likely to develop AS, that the serum level of IL-10 was higher in AS patients and that the IL17F rs763780 polymorphism can affect the levels of IL-17F in the serum of patients and controls in the same way.


Assuntos
Predisposição Genética para Doença , Interleucina-10/genética , Espondilite Anquilosante/genética , Adulto , Alelos , Brasil , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-17/sangue , Interleucina-17/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Espondilite Anquilosante/sangue , Espondilite Anquilosante/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
3.
Biomed Res Int ; 2021: 6372128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34258270

RESUMO

Introduction: This study was aimed to investigate the effects of N-acetylcysteine (NAC) on chronic obstructive pulmonary disease (COPD) and the change of Th17/Treg cytokine imbalance. Material and Methods. A total of 121 patients with stable COPD at the stage of C or D were consecutively enrolled and randomly divided into 2 groups. Patients in the treatment group received NAC granules (0.2 g × 10 bags, 0.4 g each time, 3 times/d) for half a year. The control group was treated with the same amount of placebo therapy. The peripheral blood of the patient was collected and the cytokine, T lymphocyte subsets were detected. Results: We found the oral administration of NAC could regulate Th17/Treg balance to resist inflammation in COPD patients. Serum testing showed that the proportion of Treg in CD4+ T cells has increased and the Th17/Treg ratio has decreased during the NAC treatment. In vitro studies, we found that NAC regulated Th17/Treg balance through Hypoxia Inducible Factor-1α pathway. Conclusions: Our result could provide new diagnosis and treatment for elderly patients with COPD from the perspective of immunity ideas.


Assuntos
Acetilcisteína/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/patologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Acetilcisteína/administração & dosagem , Administração Oral , Idoso , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Inflamação/sangue , Inflamação/complicações , Interleucina-10/sangue , Interleucina-17/sangue , Contagem de Linfócitos , Masculino , Doença Pulmonar Obstrutiva Crônica/sangue , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
4.
Front Immunol ; 12: 693269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220854

RESUMO

Chronic immune activation has been considered as the driving force for CD4+ T cell depletion in people infected with HIV-1. Interestingly, the normal immune profile of adult HIV-negative individuals living in Africa also exhibit chronic immune activation, reminiscent of that observed in HIV-1 infected individuals. It is characterized by increased levels of soluble immune activation markers, such as the cytokines interleukin (IL)-4, IL-10, TNF-α, and cellular activation markers including HLA-DR, CD-38, CCR5, coupled with reduced naïve and increased memory cells in CD4+ and CD8+ subsets. In addition, it is accompanied by low CD4+ T cell counts when compared to Europeans. There is also evidence that mononuclear cells from African infants secrete less innate cytokines than South and North Americans and Europeans in vitro. Chronic immune activation in Africans is linked to environmental factors such as parasitic infections and could be responsible for previously observed immune hypo-responsiveness to infections and vaccines. It is unclear whether the immunogenicity and effectiveness of anti-SARS-CoV-2 vaccines will also be reduced by similar mechanisms. A review of studies investigating this phenomenon is urgently required as they should inform the design and delivery for vaccines to be used in African populations.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Vacinas contra COVID-19/imunologia , Imunogenicidade da Vacina/imunologia , Ativação Linfocitária/imunologia , SARS-CoV-2/imunologia , ADP-Ribosil Ciclase 1/sangue , África , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/imunologia , COVID-19/prevenção & controle , Antígenos HLA-DR/sangue , Humanos , Interleucina-10/sangue , Interleucina-4/sangue , Leucócitos Mononucleares/metabolismo , Glicoproteínas de Membrana/sangue , Receptores CCR5/sangue , Fator de Necrose Tumoral alfa/sangue
5.
Front Immunol ; 12: 641879, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093531

RESUMO

Objectives: Febrile neutropenia (FN) causes treatment disruption and unplanned hospitalization in children with cancer. Serum biomarkers are infrequently used to stratify these patients into high or low risk for serious infection. This study investigated plasma abundance of cytokines in children with FN and their ability to predict bacteraemia. Methods: Thirty-three plasma cytokines, C-reactive protein (CRP) and procalcitonin (PCT) were measured using ELISA assays in samples taken at FN presentation (n = 79) and within 8-24 h (Day 2; n = 31). Optimal thresholds for prediction of bacteraemia were identified and the predictive ability of biomarkers in addition to routinely available clinical variables was assessed. Results: The median age of included FN episodes was 6.0 years and eight (10%) had a bacteraemia. On presentation, elevated PCT, IL-10 and Mip1-beta were significantly associated with bacteraemia, while CRP, IL-6 and IL-8 were not. The combination of PCT (≥0.425 ng/ml) and IL-10 (≥4.37 pg/ml) had a sensitivity of 100% (95% CI 68.8-100%) and specificity of 89% (95% CI 80.0-95.0%) for prediction of bacteraemia, correctly identifying all eight bacteraemia episodes and classifying 16 FN episodes as high-risk. There was limited additive benefit of incorporating clinical variables to this model. On Day 2, there was an 11-fold increase in PCT in episodes with a bacteraemia which was significantly higher than that observed in the non-bacteraemia episodes. Conclusion: Elevated PCT and IL-10 accurately identified all bacteraemia episodes in our FN cohort and may enhance the early risk stratification process in this population. Prospective validation and implementation is required to determine the impact on health service utilisation.


Assuntos
Bacteriemia/sangue , Neutropenia Febril/sangue , Interleucina-10/sangue , Neoplasias/sangue , Pró-Calcitonina/sangue , Bacteriemia/imunologia , Bacteriemia/microbiologia , Criança , Pré-Escolar , Neutropenia Febril/imunologia , Neutropenia Febril/microbiologia , Feminino , Humanos , Interleucina-10/imunologia , Masculino , Neoplasias/imunologia , Neoplasias/microbiologia , Valor Preditivo dos Testes , Pró-Calcitonina/imunologia
6.
Med Microbiol Immunol ; 210(4): 211-219, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34164720

RESUMO

The immune response is hypothesized as an important factor in the disease outcome of leptospirosis. Exaggerated immune response may promote tissue damage that lead to severe disease outcome. In this study TNF, IL-10, sTNFR1 levels were measured among sixty-two hospitalized leptospirosis confirmed patients in Sri Lanka. Thirty-one serum samples from healthy individuals were obtained as controls. PCR-RFLP method was used to identify TNF gene polymorphisms and to determine their association with TNF expression and disease severity in leptospirosis. TNF (p = 0.0022) and IL-10 (p < 0.0001) were found to be significantly elevated in leptospirosis patients, while sTNFR1 (p < 0.0001) was significantly suppressed. TNF was not significantly elevated in patients with complications while the anti-inflammatory cytokine IL-10 was significantly elevated among patients with complications (p = 0.0011) and with mortality (p = 0.0088). The ratio of IL-10 to TNF was higher among patients with complications (p = 0.0008) and in fatal cases (p = 0.0179). No association between TNF gene polymorphisms and TNF expression was detected due to the low frequency of heterozygous and mutated genes present in this study population. Thus the findings of the study show that elevated levels of IL-10 in the acute phase of disease could lead to severe outcomes and a high IL-10/TNF ratio is observed in patients with complications due to leptospirosis.


Assuntos
Interleucina-10/sangue , Leptospirose/sangue , Leptospirose/genética , Polimorfismo Genético , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Adulto , Citocinas/sangue , Feminino , Humanos , Interleucina-10/imunologia , Leptospirose/imunologia , Masculino , Pessoa de Meia-Idade , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia , Índice de Gravidade de Doença , Sri Lanka/epidemiologia , Fator de Necrose Tumoral alfa/imunologia
7.
Acta Trop ; 222: 106019, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34157293

RESUMO

This study detected and compared the levels of Il-17A, IFN-gamma and IL-10 in the amniotic fluid (AF) and serum of pregnant women with acute toxoplasmosis in southern Brazil. It also compared the serum levels of these mediators in pregnant women with acute or chronic toxoplasmosis and with uninfected women. The serological investigations of anti-T. gondii IgM and IgG from the 60 pregnant women were determined by chemiluminescence microparticle immunoassay (CMIA). Twenty patients were uninfected, twenty were in the chronic phase and twenty were in the acute phase of toxoplasmosis. The 20 pregnant women in acute phase all agreed with amniocentesis. Serum and AF cytokines were evaluated by sandwich enzyme-linked immunosorbent assay. The analyzed cytokines showed no significant difference in blood versus amniotic fluid levels of pregnant women in the acute toxoplasmosis. Furthermore, we observed that serum IL-17A was significantly higher in pregnant women in the acute phase of infection compared to pregnant women with chronic toxoplasmosis and seronegative pregnant women. T. gondii DNA was not amplified in any of the samples of amniotic fluid by the nested-PCR reaction. Serum IL-10 levels were also higher in negative pregnant women than in infected pregnant women. Our findings indicate the activation of an inflammatory response to infection by T. gondii and suggest that increased production of IL-17A may be a protective factor against infection of the fetus.


Assuntos
Líquido Amniótico/química , Interleucina-17/sangue , Complicações Parasitárias na Gravidez , Toxoplasmose , Anticorpos Antiprotozoários , Brasil , Feminino , Humanos , Imunoglobulina M , Interferon gama/sangue , Interleucina-10/sangue , Gravidez , Complicações Parasitárias na Gravidez/imunologia , Gestantes , Toxoplasma , Toxoplasmose/imunologia
8.
Clin Exp Rheumatol ; 39 Suppl 132(5): 22-29, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34128808

RESUMO

OBJECTIVES: We compared the serum levels of multiple cytokines in patients with adult-onset Still's disease (AOSD) and healthy controls to assess the effects of humoral factors on natural killer (NK) cells and monocytes. METHODS: We quantified the serum levels of 10 cytokines in the patients using bead-based multiplex immunoassays, along with interleukin (IL-)18 using ELISA. We then sorted NK cells and monocytes from the peripheral blood mononuclear cells (PBMCs) of healthy volunteers, cultured them in the presence or absence of cytokines that were detected in some or all of the serum samples from the AOSD patients and their combinations in vitro, and analysed the culture supernatant. RESULTS: IL-6 and IL-18 were the main cytokines increased in the serum of AOSD patients. When NK cells were cultured with the cytokines and IL-10, the combination of IL-10 and IL-18 substantially induced interferon (IFN-)γ. IL-6 had little effect on NK cells, probably because they barely expressed the IL-6 receptor and glycoprotein 130 (gp130). IFN-γ induced monocytes to produce IL-1ß, IL-6 and tumour necrosis factor (TNF-)α whereas IL-10 inhibited the induction of these proinflammatory cytokines. CONCLUSIONS: IL-10 evidently has dual effects on NK cells (stimulation) and on monocytes (inhibition). Better understanding the roles of the cytokine network would shed light on the pathogenesis of AOSD.


Assuntos
Interleucina-10/metabolismo , Doença de Still de Início Tardio , Citocinas , Humanos , Interleucina-10/sangue , Células Matadoras Naturais , Leucócitos Mononucleares , Monócitos , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológico , Doença de Still de Início Tardio/metabolismo
9.
Virol J ; 18(1): 117, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088317

RESUMO

BACKGROUND: To date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD. METHODS: The clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD. RESULTS: The ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time. CONCLUSIONS: The cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.


Assuntos
COVID-19/sangue , Síndrome da Liberação de Citocina/sangue , Citocinas/sangue , Síndrome do Desconforto Respiratório/sangue , Injúria Renal Aguda/diagnóstico , Idoso , Nitrogênio da Ureia Sanguínea , COVID-19/patologia , Creatinina/sangue , Síndrome da Liberação de Citocina/diagnóstico , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/patologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Síndrome do Desconforto Respiratório/patologia , Estudos Retrospectivos , SARS-CoV-2 , Fator de Necrose Tumoral alfa/sangue
10.
J Int Soc Sports Nutr ; 18(1): 50, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34154603

RESUMO

BACKGROUND: Acute capsaicinoid and capsinoid supplementation has endurance and resistance exercise benefits; however, if these short-term performance benefits translate into chronic benefits when combined with resistance training is currently unknown. This study investigated changes of chronic Capsiate supplementation on muscular adaptations, inflammatory response and performance in untrained men. METHODS: Twenty untrained men were randomized to ingest 12 mg Capsiate (CAP) or placebo in a parallel, double-blind design. Body composition and performance were measured at pre-training and after 6 weeks of resistance training. An acute resistance exercise session test was performed pre and post-intervention. Blood samples were collected at rest and post-resistance exercise to analyze Tumor necrosis factor- (TNF-), Soluble TNF- receptor (sTNF-r), Interleukin-6 (IL-6) and Interleukin-10 (IL-10). RESULTS: Exercise and CAP supplementation increased fat-free mass in comparison to baseline by 1.5 kg (P < 0.001), however, the majority of the increase (1.0 kg) resulted from an increase in total body water. The CAP change scores for fat-free mass were significantly greater in comparison to the placebo (CAP ∆%= 2.1 ± 1.8 %, PLA ∆%= 0.7 ± 1.3 %, P = 0.043) and there was a significant difference between groups in the bench press exercise (P = 0.034) with greater upper body strength change score for CAP (∆%= 13.4 ± 9.1 %) compared to placebo (∆%= 5.8 ± 5.2 %), P = 0.041. CAP had no effect on lower body strength and no supplementation interactions were observed for all cytokines in response to acute resistance exercise (P > 0.05). CONCLUSION: Chronic Capsiate supplementation combined with resistance training during short period (6 weeks) increased fat-free mass and upper body strength but not inflammatory response and performance in young untrained men.


Assuntos
Capsaicina/análogos & derivados , Mediadores da Inflamação/sangue , Força Muscular/efeitos dos fármacos , Treinamento de Força/métodos , Adulto , Desempenho Atlético , Composição Corporal/efeitos dos fármacos , Água Corporal/efeitos dos fármacos , Água Corporal/metabolismo , Capsaicina/administração & dosagem , Capsaicina/farmacologia , Método Duplo-Cego , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Receptores do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
11.
Cell Transplant ; 30: 9636897211024942, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34180719

RESUMO

The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-ß, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.


Assuntos
COVID-19/terapia , Transplante de Células-Tronco Mesenquimais , Adulto , Proteína C-Reativa/análise , COVID-19/patologia , COVID-19/virologia , Estado Terminal , Citocinas/sangue , Feminino , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-8/sangue , Antígenos Comuns de Leucócito/metabolismo , Linfócitos/citologia , Linfócitos/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Resultado do Tratamento
12.
Front Immunol ; 12: 637845, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995355

RESUMO

Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects of reflex physiological sympathetic activation in endotoxemic rats using bilateral carotid occlusion (BCO), a physiological approach involving the baroreflex and chemoreflex mechanisms and the influence of the baroreceptors and peripheral chemoreceptors in the cardiovascular and systemic inflammatory responses. After lipopolysaccharide (LPS) administration, the arterial pressure was recorded during 360 min in unanesthetized rats, and serial blood samples were collected to analyze the plasma cytokine levels. BCO elicited the reflex activation of the sympathetic nervous system, providing the following outcomes: (I) increased the power of the low-frequency band in the spectrum of the systolic arterial pressure during the BCO period; (II) reduced the levels of pro-inflammatory cytokines in plasma, including the tumor necrosis factor (TNF) and the interleukin (IL)-1ß; (III) increased the plasma levels of anti-inflammatory cytokine IL-10, 90 min after LPS administration. Moreover, selective baroreceptor or chemoreceptor denervation deactivated mechanosensitive and chemical sensors, respectively, and decreased the release of the LPS-induced cytokine but did not alter the BCO modulatory effects. These results show, for the first time, that physiological reflex activation of the sympathetic circuit decreases the inflammatory response in endotoxemic rats and suggest a novel function for the baroreceptors as immunosensors during the systemic inflammation.


Assuntos
Barorreflexo/fisiologia , Endotoxemia/patologia , Inflamação/fisiopatologia , Pressorreceptores/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Sistema Nervoso Autônomo/fisiologia , Pressão Sanguínea/fisiologia , Células Quimiorreceptoras/fisiologia , Interleucina-10/sangue , Interleucina-1beta/sangue , Lipopolissacarídeos , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
13.
Int J Radiat Oncol Biol Phys ; 111(2): 479-490, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33974888

RESUMO

PURPOSE: Radiation therapy (RT) modulates immune cells and cytokines, resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during RT for pediatric brain tumors and the association of these changes with therapeutic outcomes have not been well described. METHODS AND MATERIALS: The study population consisted of children (n = 83, aged 3~18) with primary brain tumors (medulloblastoma, glioma, germ cell tumors (GCT), and central nervous system embryonal tumor-not otherwise specified), with or without residual or disseminated (R/D) diseases who were starting standard postoperative focal or craniospinal irradiation (CSI). Peripheral blood T lymphocyte subsets collected before and 4 weeks after RT were enumerated by flow cytometry. Plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, and IL-17A were measured by cytometric bead array. RESULTS: Patients with R/D lesions receiving CSI (n = 32) had a post-RT increase in the frequency of CD3+T and CD8+T cells, a decrease in CD4+T cells, and an increase in regulatory T cells (Tregs) and CD8+CD28- suppressor cells, which was more predominantly seen in these patients than in other groups. In the CSI group with such R/D lesions, consisting of patients with medulloblastoma and germ cell tumors, 19 experienced a complete response (CR) and 13 experienced a partial response (PR) on imaging at 4 weeks after RT. The post/pre-RT ratio of Tregs (P = .0493), IL-6 (P = .0111), and IL-10 (P = .0070) was lower in the CR group than in the PR group. Multivariate analysis revealed that the post/pre-RT ratios of Treg, IL-6, and IL-10 were independent predictors of CR (P < .0001, P = .018, P < .0001, respectively). The areas under the receiver operating curves and confidence intervals were 0.7652 (0.5831-0.8964), 0.7794 (0.5980-0.9067), and 0.7085 (0.5223-0.8552) for IL-6, IL-10, and Treg, respectively. The sensitivities of IL-6, IL-10, and Treg to predict radiotherapeutic responses were 100%, 92.3%, and 61.5%, and specificity was 52.6%, 57.9%, and 84.2%, respectively. CONCLUSIONS: CSI treatment to those with R/D lesions predominantly exerted an effect on antitumor immune response compared with both R/D lesion-free but exposed to focal or CSI RT and with R/D lesions and exposed to focal RT. Such CSI with R/D lesions group experiencing CR is more likely to have a decrease in immunoinhibitory molecules and cells than patients who only achieve PR. Measuring peripheral blood Treg, IL-6, and IL-10 levels could be valuable for predicting radiotherapeutic responses of pediatric brain tumors with R/D lesions to CSI for medulloblastoma and intracranial germ cell tumors.


Assuntos
Neoplasias Cerebelares/radioterapia , Radiação Cranioespinal , Interleucina-10/sangue , Interleucina-6/sangue , Meduloblastoma/radioterapia , Neoplasias Embrionárias de Células Germinativas/radioterapia , Linfócitos T Reguladores/imunologia , Adolescente , Neoplasias Cerebelares/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Modelos Logísticos , Masculino , Meduloblastoma/imunologia , Meduloblastoma/patologia , Neoplasias Embrionárias de Células Germinativas/imunologia , Neoplasias Embrionárias de Células Germinativas/patologia , Subpopulações de Linfócitos T/imunologia
14.
Biomed Res Int ; 2021: 2043415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33969115

RESUMO

The protective effect of aspirin against myocardial hypertrophy (MH) was studied. Model rats of pressure overload MH were prepared by abdominal aortic coarctation. Rats were randomly divided into the sham group (n = 9), MH model group (n = 9), and MH+aspirin group (n = 9), which was, respectively, divided into the 4-week group and 8-week group according to the time of intragastric administration. Arterial blood pressure and left ventricular mass index (LVMI) were measured. Changes in myocardial tissue structure were observed by HE staining, Masson staining, and reticular fiber staining. Cardiomyocyte apoptosis was detected by TUNEL assay. The levels of TNF-α, IL-10, TXA2, and PGI2 in myocardium and plasma were detected by ELISA. The arterial blood pressure in the MH model group was significantly higher than that in the 4- and 8-week sham groups, but that in the MH+aspirin group was significantly lower than that in the MH model group. At 4 and 8 weeks, the LVWI in the MH model group was significantly higher than that in the sham group, but it was significantly reduced after aspirin treatment. The myocardial cell hypertrophy was obvious, collagen fibers were proliferated, and reticular fibers were reduced in the 4- and 8-week MH model groups. Compared with the MH model groups, myocardial cells in the MH+aspirin groups were significantly reduced, the collagen fiber content was significantly reduced, and the reticular fiber content was increased. The apoptotic cardiomyocytes in the 4- and 8-week MH model groups were obviously increased. The apoptosis of myocardial cells in the MH+aspirin groups was obviously decreased. The TNF-α levels in the myocardial tissue of the 4- and 8-week MH model groups were significantly increased, while those of the MH+aspirin groups were significantly decreased. There was no significant change in the IL-10 level or PGI2 level at 4 weeks. At 8 weeks, the PGI2 level was significantly decreased in the MH model group while significantly increased in the MH+aspirin group. The TXA2 levels were significantly increased in the 4- and 8-week MH model groups and those in the 4- and 8-week MH+aspirin groups were significantly lower. Aspirin has an anti-inflammatory effect, can effectively reduce the expression of inflammatory factors, inhibit myocardial apoptosis, and has a certain protective effect against MH.


Assuntos
Aspirina/farmacologia , Cardiotônicos/farmacologia , Miocárdio/patologia , Animais , Apoptose/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Colágenos Fibrilares/metabolismo , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Hipertrofia , Mediadores da Inflamação/metabolismo , Interleucina-10/sangue , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Tamanho do Órgão/efeitos dos fármacos , Prostaglandinas/sangue , Ratos Wistar , Tromboxano A2/sangue , Fator de Necrose Tumoral alfa/sangue
15.
Int Immunopharmacol ; 97: 107684, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33932696

RESUMO

A cell-surface heparan proteoglycan called Syndecan-1 (SDC-1) has multiple roles in healthy and pathogenic conditions, including respiratory viral infection. In this study, we explore the dynamic alternation in the levels of SDC-1 in cases with COVID-19. A total of 120 cases definitely diagnosed with COVID-19 were admitted to the Firoozgar Hospital, Tehran, Iran, from December 1, 2020, to January 29, 2021, and included in our study. Also, 58 healthy subjects (HS) were chosen as the control group. Patients were classified into two groups: 1) ICU patients and (63 cases) 2) non-ICU patients (57 cases). The dynamic changes of serum SCD-1, CRP, IL-6, IL-10, IL-18, and Vit D levels a well as the disease activity were investigated in three-time points (T1-T3). Our results indicated that the COVID-19 patients had significantly increased SCD-1, CRP, IL-6, IL-10, and IL-18 levels than in HS, while the Vit D levels in COVID-19 patients were significantly lower than HS. Further analysis demonstrated that the SCD-1, CRP, IL-6, IL-10, and IL-18 levels in ICU patients were significantly higher than in non-ICU patients. Tracking dynamic changes in the above markers indicated that on the day of admission, the SCD-1, CRP, IL-6, IL-10, and IL-18 levels were gradually increased on day 5 (T2) and then gradually decreased on day 10 (T3). ROC curve analysis suggests that markers mentioned above, SDC-1, IL-6, and IL-18 are valuable indicators in evaluating the activity of COVID-19. All in all, it seems that the serum SDC-1 levels alone or combined with other markers might be a good candidate for disease activity monitoring.


Assuntos
COVID-19/diagnóstico , Sindecana-1/sangue , Adulto , Idoso , Biomarcadores/sangue , COVID-19/mortalidade , Cuidados Críticos , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Interleucina-10/sangue , Interleucina-18/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Curva ROC , Receptores Imunológicos/sangue , Índice de Gravidade de Doença , Fatores de Tempo , Vitamina D/sangue
16.
Int Immunopharmacol ; 97: 107685, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33951560

RESUMO

BACKGROUND: The 2019 Coronavirus (COVID-19) pandemic poses a huge threat internationally; however, the role of the host immune system in the pathogenesis of COVID-19 is not well understood. METHODS: Cytokine and chemokine levels and characterisation of immune cell subsets from 20 COVID-19 cases after hospital admission (17 critically ill and 3 severe patients) and 16 convalescent patients were determined using a multiplex immunoassay and flow cytometry, respectively. RESULTS: IP-10, MCP-1, MIG, IL-6, and IL-10 levels were significantly higher in acute severe/critically ill patients with COVID-19, whereas were normal in patients who had reached convalescence. CD8 T cells in severe and critically ill COVID-19 patients expressed high levels of cytotoxic granules (granzyme B and perforin)and was hyperactivated as evidenced by the high proportions of CD38. Furthermore, the cytotoxic potential of natural killer (NK) cells, and the frequencies of myeloid dendritic cells and plasmacytoid dendritic cells was reduced in patients with severe and critical COVID-19; however, these dysregulations were found to be restored in convalescent phases. CONCLUSION: Thus, elicitation of the hyperactive cytokine-mediated inflammatory response, dysregulation of CD8 T and NK cells, and deficiency of host myeloid and plasmacytoid DCs, may contribute to COVID-19 pathogenesis and provide insights into potential therapeutic targets and strategies.


Assuntos
COVID-19/sangue , COVID-19/imunologia , Convalescença , Inflamação/etiologia , ADP-Ribosil Ciclase 1/sangue , Doença Aguda , Adulto , Idoso , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/enzimologia , Linfócitos T CD8-Positivos/imunologia , Quimiocina CCL2/sangue , Quimiocina CXCL10/sangue , Quimiocina CXCL9/sangue , Estado Terminal , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/imunologia , Células Dendríticas/imunologia , Feminino , Granzimas/metabolismo , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Células Matadoras Naturais/enzimologia , Células Matadoras Naturais/imunologia , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Perforina/metabolismo
17.
Trop Biomed ; 38(1): 187-204, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33797545

RESUMO

Malaria infection still remains as one of the most prominent parasitic diseases afflicting mankind in tropical and subtropical regions. The severity of malaria infection has often been associated to exuberant host immune inflammatory responses that could possibly lead to severe immunopathological conditions and subsequent death of host tissues. Activin A is a protein belonging to the transforming growth factor-beta (TGF-ß) family that regulates multiple physiological processes and pathological-associated diseases. The biological roles of activin A have been associated with manipulation of inflammation-related processes and modulation of host immune responses. This implies that activin A protein could play a role in malaria pathogenesis since malaria infection has been closely linked to severe immune responses leading to death, However, the actual in vivo role of activin A in malaria infection remains elusive. Hence, this study was undertaken to investigate the involvement of activin A in malaria infection as well as to assess the modulating effects of activin A on the cytokine releases (TNF-α, IFN-γ and IL-10) and histopathological changes in major affected organs (kidney, liver, lung, brain and spleen) in malarial mice infected with Plasmodium berghei ANKA. Our results showed that the concentrations of plasma activin A were significantly increased in malarial mice throughout the study periods. Also. the systemic activin A level was positively correlated with malaria parasitemia. This indicates that activin A could play a role in malaria pathogenesis and malaria parasitemia development. Plasma TNF-α, IFN-γ and IL-10 cytokine levels were significantly increased in malarial mice at day-5 post infection, suggesting that these cytokines attributed to severe malaria pathogenesis. Histopathological features such as sequestration of parasitized red blood cells (pRBCs) and hemozoin formation were amongst the most common pathological conditions observed in tissues of major affected organs (kidney, liver, lung, brain and spleen) in malarial mice. Neutralization of activin A production via recombinant mouse activin RIIA Fc chimera (rmActivin RIIA Fc chimera) had significantly reduced the parasitemia levels in malarial mice. The release of TNF-α cytokine was significantly reduced as well as the sequestration of parasitized pRBCs and hemozoin formation in major affected organs in malarial mice were also alleviated following inhibition of activin A production. Overall, this preliminary study suggests that activin A could play an immune modulation role in malaria pathogenesis through modulation of TNF-α release that benefits host from severe pathological destructions provoked by intensified inflammatory responses. Further studies are warranted to elucidate the precise mechanism of immune modulation mediated by activin A and its associated immune-modulation mediators in regulating the inflammatory responses elicited during the course of malaria infection.


Assuntos
Ativinas/antagonistas & inibidores , Malária/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue , Ativinas/imunologia , Animais , Citocinas/sangue , Interferon gama/sangue , Interleucina-10/sangue , Malária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Plasmodium berghei
18.
BMC Cardiovasc Disord ; 21(1): 194, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879070

RESUMO

BACKGROUND: Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension and the resulting target organ damage. In this study, we observed alterations in the monocyte phenotype and inflammatory state of hypertensive patients with left ventricular hypertrophy (LVH) and studied the effects of irbesartan in these patients. This study might reveal a novel mechanism by which irbesartan alleviates LVH, and it could provide new targets for the prevention and treatment of hypertensive target organ damage. METHODS: CD163 and CD206 expression on monocytes and IL-10 and TNF-α levels in the serum of hypertensive patients with or without LVH and of healthy volunteers were detected. Furthermore, we treated monocytes from the LVH group with different concentrations of irbesartan, and then, CD163, CD206, IL-10 and TNF-α expression was detected. RESULTS: We found, for the first time, that the expression of CD163, CD206 and IL-10 in the LVH group was lower than that in the non-LVH group and healthy control group, but the TNF-α level in the LVH group was significantly higher. Irbesartan upregulated the expression of CD163 and CD206 in hypertensive patients with LVH in a concentration-dependent manner. Irbesartan also increased the expression of IL-10 and inhibited the expression of TNF-α in monocyte culture supernatants in a concentration-dependent manner. CONCLUSIONS: Our data suggest that inflammation was activated in hypertensive patients with LVH and that the monocyte phenotype was mainly proinflammatory. The expression of proinflammatory factors increased while the expression of anti-inflammatory factors decreased. Irbesartan could alter the monocyte phenotype and inflammatory status in hypertensive patients with LVH. This previously unknown mechanism may explain how irbesartan alleviates LVH. Trail registration The study protocols were approved by the Ethical Committee of the Second Affiliated Hospital of Dalian Medical University. Each patient signed the informed consent form.


Assuntos
Anti-Inflamatórios/farmacologia , Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/prevenção & controle , Irbesartana/farmacologia , Monócitos/efeitos dos fármacos , Idoso , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Pressão Sanguínea , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Interleucina-10/sangue , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Monócitos/metabolismo , Fenótipo , Receptores de Superfície Celular/sangue , Receptores Imunológicos/sangue , Fator de Necrose Tumoral alfa/sangue , Função Ventricular Esquerda , Remodelação Ventricular
19.
Ann Clin Biochem ; 58(5): 434-444, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33827266

RESUMO

BACKGROUND: Recently, studies on COVID-19 have focused on the epidemiology of the disease and clinical characteristics of patients, as well as on the risk factors associated with mortality during hospitalization in critical COVID-19 cases. However, few research has been performed on the prediction of disease progression in particular group of patients in the early stages of COVID-19. METHODS: The study included 338 patients with COVID-19 treated at two hospitals in Wuhan, China, from December 2019 to March 2020. Predictors of the progression of COVID-19 from mild to severe stages were selected by the logistic regression analysis. RESULTS: COVID-19 progression to severe and critical stages was confirmed in 78 (23.1%) patients. The average value of the neutrophil-to-lymphocyte ratio (NLR) was higher in patients in the disease progression group than in the improvement group. Multivariable logistic regression analysis revealed that elevated NLR, LDH and IL-10 were independent predictors of disease progression. The optimal cut-off value of NLR was 3.75. The values of the area under the curve, reflecting the accuracy of predicting COVID-19 progression by NLR was 0.739 (95%CI: 0.605-0.804). The risk model based on NLR, LDH and IL-10 had the highest area under the ROC curve. CONCLUSIONS: The performed analysis demonstrates that high concentrations of NLR, LDH and IL-10 were independent risk factors for predicting disease progression in patients at the early stage of COVID-19. The risk model combined with NLR, LDH and IL-10 improved the accuracy of the prediction of disease progression in patients in the early stages of COVID-19.


Assuntos
COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Adulto , Idoso , COVID-19/sangue , COVID-19/imunologia , China/epidemiologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Interleucina-10/sangue , L-Lactato Desidrogenase/sangue , Modelos Logísticos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pontuação de Propensão , Fatores de Risco
20.
Acta Trop ; 219: 105915, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33861971

RESUMO

This study investigated the participation extracellular vesicles (EVs) in Toxoplasma gondii-host interaction. EVs of three T. gondii strains (RH, ME-49 and VEG) were purified by chromatography and ELISA. Results of "nanoparticle tracking analysis" and scanning electron microscopy showed that RH strain released more EVs than other strains. Images of transmission electron microscopy showed that in beginning of incubation (culture medium), EVs were inside of tachyzoites preparing to be released. After 24 hours, they were largely produced inside tachyzoites and were released through plasma membrane. The parasite burden of mice infected with RH strain plus EVs was increased and with early death of 1-2 days compared of those that received only parasites. EV proteins of ME-49 and VEG strains were poorly reactive to sera of infected patients in imunoblot. However, those from RH strain were reactive against sera of patients with cerebral toxoplasmosis. EVs stimulated murine splenocytes caused similar production of IFN-γ and IL-10 levels. RH strain derived EVs stimulated more TNF-α than those stimulated by other strains. T. gondii and infected hosts can express the same miRNAs (miR-155-5p, miR-125b-5p, miR-423-3p). In conclusion, T. gondii derived EVs promote host-parasite interactions, modulate host immune responses, carry virulent factors and cause an imbalance in cellular immune response.


Assuntos
Vesículas Extracelulares/metabolismo , Toxoplasma/citologia , Animais , Humanos , Imunidade Celular , Interleucina-10/sangue , Camundongos , MicroRNAs/sangue , Toxoplasma/imunologia , Toxoplasmose Animal/imunologia , Fator de Necrose Tumoral alfa/sangue
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