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1.
Biomed Res Int ; 2022: 2755246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35540724

RESUMO

Background: To investigate the association between interleukins (IL-1ß, IL-2, IL-4, IL-6, IL-8, and IL-10) and the disease severity of coronavirus disease 2019 (COVID-19). Materials and Methods: We systematically searched records investigating the role of interleukins (IL-1ß, IL-2, IL-4, IL-6, IL-8, and IL-10) in COVID-19 patients in Web of Science, Pubmed, and Embase through December 2020. Data were extracted and pooled, and the weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated. The funnel plot and the nonparametric trim and fill method were used to visualize and adjust the publication bias. Results: In total, 61 studies enrolled 14,136 subjects (14,041 patients and 95 healthy subjects) were enrolled in this meta-analysis. Our results showed that serum IL-2, IL-4, IL-6, and IL-10 levels were elevated in COVID-19 patients compared to healthy controls, and IL-6, IL-8, and IL-10 levels were increased in severe COVID-19 cases compared to nonsevere patients. Additionally, the levels of IL-1ß, IL-6, and IL-8 were elevated in nonsurvivor patients compared to survivors. For patients in the intensive care unit (ICU), IL-6 and IL-8 levels were increased than that in non-ICU patients. Conclusions: Elevated levels of IL-6, IL-8, and IL-10 were associated with the disease severity of COVID-19, and elevated levels of IL-1ß, IL-6, and IL-8 were related to the prognosis of COVID-19 patients, which could be used to evaluate COVID-19 patients' disease severity and prognosis.


Assuntos
COVID-19 , Interleucinas , COVID-19/sangue , Humanos , Interleucinas/sangue , Índice de Gravidade de Doença
2.
PLoS Negl Trop Dis ; 16(4): e0010308, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35421083

RESUMO

Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and, consequently, the possibility of immune-mediated interactions among different parasite species. Intestinal protozoa and helminths could modulate antimalarial immunity, for example, thereby potentially increasing or reducing susceptibility to malaria. The aim of the study was to compare the cytokine levels and cytokine ratios according to parasitic profiles of the population to determine the potential role of co-endemic parasites in the malaria susceptibility of populations. Blood and stool samples were collected during cross-sectional surveys in five provinces of Gabon. Parasitological diagnosis was performed to detect plasmodial parasites, Loa loa, Mansonella perstans, intestinal helminths (STHs) and protozoan parasites. Nested PCR was used to detect submicroscopic plasmodial infection in individuals with negative blood smears. A cytometric bead array was used to quantify interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α in the plasma of subjects with different parasitological profiles. Median IL-6 and IL-10 levels and the median IL-10/TNF-α ratio were all significantly higher among individuals with Plasmodium (P.) falciparum infection than among other participants (p<0.0001). The median TNF-α level and IL-10/IL-6 ratio were higher in subjects with STHs (p = 0.09) and P. falciparum-intestinal protozoa co-infection (p = 0.04), respectively. IL-6 (r = -0.37; P<0.01) and IL-10 (r = -0.37; P<0.01) levels and the IL-10/TNF-α ratio (r = -0.36; P<0.01) correlated negatively with age. Among children under five years old, the IL-10/TNF-α and IL-10/IL-6 ratios were higher in those with intestinal protozoan infections than in uninfected children. The IL-10/TNF-α ratio was also higher in children aged 5-15 years and in adults harbouring blood-borne filariae than in their control counterparts, whereas the IL-10/IL-6 ratio was lower in those aged 5-15 years with filariae and intestinal parasites but higher in adults with intestinal parasitic infections. Asymptomatic malaria is associated with a strong polarization towards a regulatory immune response, presenting high circulating levels of IL-10. P. falciparum/intestinal protozoa co-infections were associated with an enhanced IL-10 response. Immunity against malaria could differ according to age and carriage of other parasites. Helminths and intestinal protozoa can play a role in the high susceptibility to malaria currently observed in some areas of Gabon, but further investigations are necessary.


Assuntos
Coinfecção , Interleucinas , Malária Falciparum , Malária , Animais , Pré-Escolar , Cidades/epidemiologia , Coinfecção/epidemiologia , Coinfecção/parasitologia , Estudos Transversais , Citocinas/sangue , Gabão/epidemiologia , Humanos , Interleucinas/sangue , Malária/sangue , Malária/epidemiologia , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Plasmodium falciparum/isolamento & purificação , População Rural/estatística & dados numéricos , Fator de Necrose Tumoral alfa/sangue
3.
Sci Rep ; 12(1): 5458, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361913

RESUMO

Type III interferons (IFNs) play an important role in respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to determine whether the expression of serum type III IFNs predicted disease severity among patients with the coronavirus disease (COVID-19). A retrospective cohort study was conducted of patients admitted to a single hospital between March 21, 2020, and March 31, 2021. Patients were divided into mild to moderate I (MM) and moderate II to severe (MS) groups based on the COVID-19 severity classification developed by the Japanese Ministry of Health, Labor and Welfare. A total of 257 patients were included in the analysis. Human interleukin-28A (IL-28A/IFN-λ2) expression was significantly lower, and interleukin (IL)-6 expression was significantly higher in the MS group than in the MM group (both p < 0.001). In addition, IL-28A/IFN-λ2 was statistically significantly inversely correlated with the time from disease onset to negative SARS-CoV-2 PCR results (p = 0.049). Multivariable logistic regression analysis showed that IL-28A/IFN-λ2 was an independent predictor of disease severity (p = 0.021). The low expression of IL-28A/IFN-λ2 may serve as a serum biomarker that predicts the severity of COVID-19, possibly through the mechanism of delayed viral elimination.


Assuntos
COVID-19 , Interleucinas , COVID-19/diagnóstico , COVID-19/imunologia , Citocinas , Humanos , Interleucinas/sangue , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença
4.
Arthritis Res Ther ; 24(1): 86, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428323

RESUMO

BACKGROUND: We explored whether serum cytokines could be used as biomarkers for optimal use of tumor necrosis factor inhibitors (TNF-i) and interleukin (IL)-17 inhibitors (IL-17-i) in patients with psoriatic arthritis (PsA). METHODS: In cohort 1 (47 patients treated with IL-17-i [n=23] or TNF-i [n=24] for ≥1 year), we identified serum cytokines that predicted the achievement of Disease Activity in Psoriatic Arthritis-remission (DAPSA-REM), Psoriasis Area and Severity Index (PASI) 90, and Minimal Disease Activity after 1 year of TNF-i or IL-17-i therapy. Subsequently, we developed treatment strategies based on the identified cytokines; initiation of IL-17-i therapy in patients with low IL-22 concentrations (IL-22 <0.61376 pg/ml) and TNF-i therapy in patients with high IL-22 concentrations (0.61376< IL-22 pg/ml). In cohort 2 (34 patients), treatment responses were compared between the strategic treatment group (n=17), which was treated based on the treatment strategies, and the mismatched treatment group (n=17) to verify the validity of the treatment strategies developed using serum cytokines as biomarkers. RESULTS: In cohort 1, serum IL-22 concentration was identified as a predictor of DAPSA-remission after 1 year of IL-17-i therapy. Regarding treatment strategies, we selected TNF-i for patients with high IL-22 concentrations and IL-17-i for those with low IL-22 concentrations. There were no significant differences in the baseline characteristics between the strategic and mismatched treatment groups. Regarding treatment effects, activity significantly improved at 1 year in both groups. Upon comparison of the treatment effects, the rate of achieving DAPSA-REM and Minimal Disease Activity at month 12 was significantly higher in the strategic treatment group. CONCLUSIONS: The results of this pilot study suggest that IL-22 may be a biomarker of treatment response to TNF-i and IL-17-i in patients with PsA. Further large-scale studies in independent, prospectively collected datasets are required to verify that IL-22 is indeed a biomarker of treatment response in these patients.


Assuntos
Antirreumáticos , Artrite Psoriásica , Interleucinas , Antirreumáticos/uso terapêutico , Artrite Psoriásica/sangue , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Biomarcadores/sangue , Citocinas/sangue , Humanos , Interleucina-17/sangue , Interleucinas/sangue , Masculino , Terapia de Alvo Molecular , Projetos Piloto , Antígeno Prostático Específico/sangue , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Toxins (Basel) ; 14(3)2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35324695

RESUMO

Chronic-kidney-disease-associated pruritus (CKD-aP) is one of the most common and burdensome dermatological symptoms affecting patients undergoing dialysis, and its etiopathogenesis has still not been fully discovered. This study was designed to investigate the possible contribution of interleukin-31 (IL-31) to the pathogenesis of itch in patients undergoing maintenance hemodialysis (HD). We evaluated the serum level of IL-31 in HD patients with pruritus, in HD patients without pruritus and in healthy controls, as well as its correlation to the severity of itch. The study enrolled 175 adult subjects. The participants were divided into three groups. Group A included 64 patients on maintenance HD with CKD-aP, Group B included 62 patients on maintenance HD not reporting CKD-aP and Group C included 49 healthy controls. Pruritus severity was assessed using the Numerical Rating Scale (NRS), and the serum levels of IL-31 were measured. The results showed that the IL-31 serum level was significantly higher in the itchy group (p < 0.001) in comparison to the patients free from pruritus. Moreover, a marginal trend towards significance (r = 0.242, p = 0.058) was observed between the IL-31 serum level and itch intensity. Our study supports earlier findings on the extended role of IL-31 in the development of CKD-aP.


Assuntos
Interleucinas , Falência Renal Crônica , Insuficiência Renal Crônica , Adulto , Feminino , Humanos , Interleucinas/sangue , Falência Renal Crônica/diagnóstico , Masculino , Prurido/etiologia , Diálise Renal , Insuficiência Renal Crônica/complicações
6.
Arq Bras Cardiol ; 118(2): 400-408, 2022 02.
Artigo em Inglês, Português | MEDLINE | ID: mdl-35262572

RESUMO

BACKGROUND: It has been shown that interleukin-35 (IL-35) subunits are strongly expressed in atherosclerotic plaques in humans. Therefore, it is considered to play a role in atherosclerosis. OBJECTIVES: In this study, IL-35 levels were compared with the control group in patients with stable coronary artery disease (CAD), and the association between IL-35 levels and the lesion type, lesion severity and extension was investigated with the Gensini score (GS) and the Syntax score (SS) in the patient group. METHODS: Sixty patients (18 female and 42 male) with CAD diagnosed by coronary angiography, who presented with typical chest pain and positive noninvasive cardiac stress test, and 46 patients (18 female and 28 male) with normal coronary lumenogram, were included in this study. Gensini and Syntax scores were calculated in the patient group, and these values were compared with IL-35 levels. Non-normally distributed variables were analyzed by the Mann-Whitney U test, whereas normally distributed parameters were assessed by Student's t-test. The difference between categorical variables were evaluated by the Chi-square or Fisher test. P-values<0.05 were considered as statistically significant. RESULTS: No significant differences were observed between patients and the control group in terms of demographic characteristics and laboratory findings. Compared to the control group, IL-35 levels of the CAD group were considerably lower (36.9±63.9 ng/ml vs. 33.2±13.2 ng/ml, p<0.008). Although not statistically significant, IL-35 levels were higher in patients with low SS than among those with high SS (33.2±13.7 vs. 31.8±8.9, p=0.51). The IL-35 values of the patients with high GS were significantly lower than in patients with low GS (35±17.4 vs. 30.7±8.6, p=0.043). CONCLUSION: It has been shown that IL-35 levels can be a new biomarker for stable CAD, and IL-35 is associated with the extension of CAD.


FUNDAMENTO: Foi demonstrado que as subunidades de interleucina-35 (IL-35) estão fortemente expressas nas placas ateroscleróticas em humanos. Assim, considera-se que elas têm um papel na aterosclerose. OBJETIVOS: Neste estudo, os níveis de IL-35 foram comparados com o grupo controle em pacientes com doença arterial coronariana (DAC) estável, e a associação entre os níveis de IL-35 e o tipo, gravidade e extensão da lesão foram investigadas com o escore Gensini (GS) e o escore Syntax (SS) no grupo de pacientes. MÉTODOS: Sessenta pacientes (18 mulheres e 42 homens) com DAC, diagnosticados por meio da angiografia coronária, que apresentaram dor no peito típica e teste de esforço não invasivo positivo, e 46 pacientes (18 mulheres e 28 homens) com luminograma normal, foram incluídos no estudo. Tanto o GS quanto o SS foram calculados para o grupo de pacientes, e esses valores foram comparados com os níveis de IL-35. Variáveis com distribuição não normal foram avaliadas com o teste U de Mann-Whitney, enquanto os parâmetros com distribuição normal foram analisados com o teste t de Student. A diferença entre as variáveis categóricas foi avaliada pelo teste de qui-quadrado ou de Fisher. Os valores de p<0,05 foram considerados como estatisticamente sinificativos. RESULTADOS: Não foram observadas diferenças significativas entre pacientes e o grupo controle em termos de características demográficas e achados laboratoriais. Em comparação ao grupo controle, os níveis de IL-35 no grupo com DAC foram consideravalmente menores (36,9±63,9 ng/ml vs. 33,2±13,2 ng/ml, p<0,008). Embora não tenha sido estatisticamente significativo, os níveis de IL-35 foram maiores em pacientes com SS mais baixo do que nos com SS mais alto (33,2±13,7 vs. 31,8±8,9, p=0,51). Os valores de IL-35 em pacientes com GS alto foram significativamente mais baixos do que em pacientes com GS baixo (35±17,4 vs. 30,7±8,6, p=0,043). CONCLUSÃO: Demonstrou-se que os níveis de IL-35 podem ser um novo biomarcador para a DAC estável, e que a IL-35 está associada à extensão da DAC.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Interleucinas , Aterosclerose/diagnóstico , Biomarcadores , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Feminino , Humanos , Interleucinas/sangue , Masculino , Índice de Gravidade de Doença
7.
J Clin Lab Anal ; 36(4): e24284, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35182078

RESUMO

BACKGROUND: Interleukin (IL)-39 is a novel member of IL-12 cytokine family, but its role in autoimmune thyroid diseases (AITD) is unclear. The aim of the present study was to determine serum levels of IL-39 in Hashimoto's thyroiditis (HT) and Graves' disease (GD) patients. METHODS: A total of 48 patients with HT, 50 patients with GD, and 45 healthy controls (HCs) were recruited for this study. Levels of serum IL-39 were determined by ELISA. RESULTS: Compared with HC group, levels of serum IL-39 in patients with HT (p < 0.05) and GD (p < 0.01) were drastically reduced. Among patients with HT, serum IL-39 levels had a positive correlation with white blood cell count (WBC) count and free triiodothyronine level. Among patients with GD, the levels of IL-39 in serum were positively correlated with WBC count and C-reactive protein levels. CONCLUSIONS: IL-39 may be a new potential predictor for patients with HT and GD.


Assuntos
Doença de Graves , Doença de Hashimoto , Interleucinas , Estudos de Casos e Controles , Doença de Graves/sangue , Doença de Hashimoto/sangue , Humanos , Interleucinas/sangue , Tri-Iodotironina/sangue
8.
J Obstet Gynaecol Res ; 48(4): 973-979, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35199410

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in females of reproductive age, with a prevalence of 20%-33% in the general population. Interleukin (IL)-34 is a recently explored proinflammatory cytokine and is an important modulator in different disease types. However, the function of IL-34 in PCOS has yet to be investigated. OBJECTIVE: The purpose of this study was to determine the IL-34 serum level in women with PCOS and to compare it to that of a relatively healthy control group. Focusing on its relationship with IL-6, TNF-α, and IL-1ß and homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, and low-density lipoprotein cholesterol (LDL-C). MATERIALS AND METHODS: In this study, blood samples were obtained from 100 women with PCOS and 100 healthy control women for the purpose of estimating their serum levels of IL-34, IL-6, TNF-α, and IL-1ß using the enzyme-linked immunosorbent assay technique. RESULTS: Serum levels of IL-34, IL-6, TNF-α, and IL-1ß were all higher in PCOS women than in healthy controls, and the difference was highly statistically significant. Serum IL-34 concentration was positively correlated with IL-6, TNF-α, and IL-1ß concentration. Additionally, serum concentrations of IL-34 were positively correlated with HOMA-IR, triglyceride, and LDL-C. CONCLUSION: When compared to normal women, IL-34, IL-6, TNF-α, and IL-1ß levels were highly statistically significant in PCOS, and these high levels were associated with other cytokines (IL-6, TNF-α, and IL-1ß), HOMA-IR, triglyceride, and LDL-C.


Assuntos
Resistência à Insulina , Interleucinas , Síndrome do Ovário Policístico , Biomarcadores , Índice de Massa Corporal , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Humanos , Interleucinas/sangue , Síndrome do Ovário Policístico/complicações
9.
FASEB J ; 36(3): e22180, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35129860

RESUMO

P75 pan-neurotrophin receptor (p75NTR) is an important receptor for the role of neurotrophins in survival and death of neurons during development and after nerve injury. Our previous research found that the precursor of brain-derived neurotrophic factor (proBDNF) regulates pain as an inflammatory mediator. The current understanding of the role of proBDNF/p75NTR signaling pathway in inflammatory arthritis pain and rheumatoid arthritis (RA) is unclear. We recruited 20 RA patients, 20 healthy donors (HDs), and 10 osteoarthritis (OA) patients. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of proBDNF and p75NTR in synovial membrane were performed and evaluated. We next examined the mRNA and protein expression of proBDNF/p75NTR signaling pathway in peripheral blood mononuclear cells (PBMCs) and synovial tissue. ELISA and flow cytometry were assessed between the blood of RA patients and HD. To induce RA, collagen-induced arthritis (CIA) were induced in mice. We found over-synovitis of RA synovial membrane compared to OA controls in histologic sections. P75NTR and sortilin mRNA, and proBDNF protein level were significantly increased in PBMCs of RA patients compared with the HD. Consistently, ELISA showed that p75NTR, sortilin, tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels in the serum of RA patients were increased compared with HD and p75NTR, sortilin were positively correlated with Disease Activity Score in 28 joints (DAS28). In addition, using flow cytometry we showed that the increased levels of proBDNF and p75NTR characterized in CD4+ and CD8+ T cells of RA patients were subsequently reversed with methotrexate (MTX) treatment. Furthermore, we found pathological changes, inflammatory pain, upregulation of the mRNA and protein expression of proBDNF/p75NTR signaling pathway, and upregulation of inflammatory cytokines in spinal cord using a well-established CIA mouse model. We showed intravenous treatment of recombinant p75ECD-Fc that biologically blocked all inflammatory responses and relieved inflammatory pain of animals with CIA. Our findings showed the involvement of proBDNF/p75NTR pathway in the RA inflammatory response and how blocking it with p75ECD-Fc may be a promising therapeutic treatment for RA.


Assuntos
Artrite Reumatoide/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Interleucinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Animais , Feminino , Humanos , Interleucinas/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Precursores de Proteínas/metabolismo , Membrana Sinovial/metabolismo , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/sangue
10.
Nutr Hosp ; 39(2): 313-319, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35156380

RESUMO

Introduction: Background: many genes have been involved in the development of obesity. Interleukin 32 (IL-32) is a proinflammatory cytokine; rs45499297 is a T/C promoter, single-nucleotide polymorphism of the IL32 gene. Objectives: this study aimed to evaluate the rs45499297 polymorphism and its association with obesity. Another objective of this study was to carry out an in silico analysis. Methods: this study was cross-sectional, and included 333 subjects classified by body mass index and fat percentage. The plasma glucose and lipid profile were measured. We measured serum IL-32 protein by ELISA and the rs45499297 polymorphism by PCR-RFLP. We used several databases to build the IL32 gene network and infer transcription factors that bind to this polymorphic site. Results: subjects underweight and with low fat percentages had lower levels of IL-32. CT genotype and allele C were less frequent in the overweight/obesity group than in the normal-weight group. Interestingly, this result remained only in the male gender. We found that the transcription factors Hepatocyte Nuclear Factor and Specificity Protein 1 bind to this polymorphic site. In addition, we infer that IL32 is involved in metabolic pathways related to viral infections. Conclusion: the TC genotype is associated with overweight/obesity. The decrease in levels of IL-32 observed in underweight and low fat percentage groups could be due to an impaired inflammatory profile. The in silico analysis showed that several transcriptional factors bind at this polymorphic site, and that the enrichment of the metabolic pathways is diverse.


Introducción: Introducción: la interleucina 32 es una citocina proinflamatoria. El rs45499297 es un polimorfismo de nucleótido simple del gen de IL32, situado en la región promotora y caracterizado por un cambio de T/C. Objetivo: evaluar el polimorfismo rs45499297 y su asociación con la obesidad, y realizar un análisis in silico. Métodos: el estudio fue transversal e incluyó 333 sujetos clasificados por índice de masa corporal y porcentaje de grasa. Se midieron la glucosa y el perfil lipídico, así como los niveles séricos de IL-32 mediante ELISA y el genotipo del polimorfismo rs45499297 mediante PCR-RFLP. Para el análisis in silico se utilizaron varias bases de datos para hacer la red de genes de IL32 e inferir factores de transcripción unidos al sitio polimórfico. Resultados: los sujetos con bajo peso y bajo porcentaje de grasa tienen niveles más bajos de IL-32. El genotipo TC y el alelo C se encontraron con menos frecuencia en los sujetos con sobrepeso/obesidad que en los normopeso, resultado que permaneció solo en el género masculino. Se encontró que el factor nuclear de los hepatocitos y la proteína de especificidad 1 se unen a este sitio polimórfico. Se infiere que IL32 está involucrado en vías metabólicas relacionadas con las infecciones virales. Conclusión: el genotipo TC está asociado al sobrepeso/la obesidad. La disminución de los niveles de IL-32 observada en los sujetos con bajo peso y bajo porcentaje de grasa podría ser por un perfil inflamatorio alterado. El análisis in silico mostró que varios factores de transcripción se unen al sitio polimórfico y que el enriquecimiento de las vías metabólicas es diverso.


Assuntos
Interleucinas , Obesidade , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Humanos , Interleucinas/sangue , Interleucinas/genética , Masculino , México/epidemiologia , Polimorfismo de Nucleotídeo Único
11.
Indian J Pathol Microbiol ; 65(1): 111-116, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35074974

RESUMO

BACKGROUND: : Many biomarkers have now been studied such as C-reactive Protein (CRP), procalcitonin (PCT), etc., and are widely used for the diagnosis of sepsis in clinical practice which may determine the appropriate antibiotic treatment. A flowcytometric cytokine bead array (CBA) assay has now been used to determine multiple interleukins (IL), simultaneously. The aim of this study was to determine the cytokine (IL2, IL4, IL6, IL10, TNFα, INFγ, and IL17) profiles of interleukins in plasma of sepsis patients by using multiplex Flowcytometric CBA array assay. MATERIALS AND METHOD: s: A total of 99 consecutive patients admitted with the suspected sepsis were studied. PCT concentrations were measured by using the enzyme-linked fluorescent immunoassay (ELFA) technique and flow cytometry-based BD™ CBA Cytokine Kit was used to evaluate levels of 7 cytokines [IL-2, IL-4, IL-6, IL-10, Tumour Necrosis Factor (TNF), Interferon- γ (IFN-γ), and IL-17A]. RESULTS: Microbiologically defined infection (MDI) demonstrated a positive culture report in 79/99 (79.7%) of patients. The IL6 [1873.7 (4-5000)] and IL10 [(154.7 (0-1764)] levels were significantly higher in septic patients than those in the negative MDI IL6 [901 (4-5000)] and IL10 [110.4 (4-1372)] levels. The AUROC value of IL6 [0.66 (0.53-0.79)] was found to be the highest among all followed by IL10 [0.65 (0.51-0.79)], IFNγ [0.63 (0.51-0.77)], PCT [0.61 (0.48-0.75)], and TNFα [0.55 (0.42-0.69)]. CONCLUSION: Our study suggests that that IL6 is substantially more economical and can reduce the investigation cost to half as compared with the procalcitonin assay.


Assuntos
Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Interleucinas/sangue , Pró-Calcitonina/sangue , Sepse/diagnóstico , Biomarcadores/sangue , Estado Terminal , Humanos , Curva ROC , Sepse/imunologia , Atenção Terciária à Saúde/estatística & dados numéricos
12.
Nutrients ; 14(2)2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35057459

RESUMO

The effects of synbiotic yogurt supplemented with inulin on the pathological manifestations and gut microbiota-bile acid axis were investigated using a dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) mice model. Female C57BL/6J mice were injected subcutaneously with DHEA at a dose of 6 mg/100 g BW for 20 days to establish a PCOS mouse model. Then, the PCOS mice were treated with yogurt containing inulin (6% w/w) at 15 mL/kg BW for 24 days. Results showed that supplementation of synbiotic yogurt enriched with inulin to PCOS mice decreased the body weight gain, improved estrus cycles and ovary morphology, and reduced the levels of luteinizing hormone while increasing the levels of follicle-stimulating hormone and interleukin-22 in serum. At the genus level, synbiotic yogurt increased the relative abundance of Lactobacillus, Bifidobacterium, and Akkermansia. PICRUSt analysis indicated that KEGG pathways including bile acid biosynthesis were changed after inulin-enriched synbiotic yogurt supplementation. Synbiotic yogurt enriched with inulin also modulated the bile acid profiles. In conclusion, inulin-enriched synbiotic yogurt alleviated reproductive dysfunction and modulated gut microbiota and bile acid profiles in PCOS mice.


Assuntos
Microbioma Gastrointestinal , Inulina/administração & dosagem , Síndrome do Ovário Policístico/dietoterapia , Simbióticos/administração & dosagem , Iogurte , Adjuvantes Imunológicos , Akkermansia , Animais , Bifidobacterium , Ácidos e Sais Biliares/análise , Ácidos e Sais Biliares/biossíntese , Peso Corporal/fisiologia , Desidroepiandrosterona , Estro/fisiologia , Feminino , Hormônio Foliculoestimulante/sangue , Interleucinas/sangue , Lactobacillus , Hormônio Luteinizante/sangue , Camundongos , Camundongos Endogâmicos C57BL , Ovário/anatomia & histologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/induzido quimicamente
13.
J Diabetes Complications ; 36(3): 108133, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35090823

RESUMO

IL-38 is a recently discovered, novel anti-inflammatory cytokine, which belongs to the IL-1ß family. The role played by this cytokine in diabetes-tuberculosis nexus is not known. Serum levels of IL-38, TNF-α, IL-6, and IL-1ß in Normal Glucose Tolerance (NGT) and chronic Diabetes (DM) subjects, both with and without latent tuberculosis (LTB) (n = 256) were quantified by ELISA. While, serum levels of IL-38 were significantly reduced, the levels of TNF-α, IL-6, and IL-1ß were not altered, in LTB infected diabetes patients. While no significant secretion of IL-38 was detected in the quantiferon supernatant, secretion of TNF-α, IL-6, and IL-1ß was significantly reduced in LTB infected diabetes patients. The decreased systemic levels of IL-38 and reduced in vitro secretion of other pro-inflammatory cytokines might represent a crucial pathway associated with diabetes-tuberculosis nexus.


Assuntos
Citocinas , Diabetes Mellitus , Interleucinas , Tuberculose Latente , Citocinas/sangue , Complicações do Diabetes/imunologia , Diabetes Mellitus/sangue , Diabetes Mellitus/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Interleucinas/sangue , Interleucinas/imunologia , Tuberculose Latente/sangue , Tuberculose Latente/complicações , Tuberculose Latente/imunologia , Fator de Necrose Tumoral alfa
14.
Cytokine ; 151: 155804, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35063722

RESUMO

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disorder caused by a new coronavirus called SARS-CoV-2. The pathophysiology of severe COVID-19 is associated with a "cytokine storm". IL-32 is a key modulator in the pathogenesis of various clinical conditions and is mostly induced by IL-8. IL-32 modulates important inflammatory pathways (including TNF-α, IL-6 and IL-1b), contributing to the pathogenesis of inflammatory diseases. Il-32 was never evaluated before in COVID-19 patients stratifying as mild-moderate and severe patients. A total of 64 COVID-19 patients, 27 healthy controls were consecutively enrolled in the study. Serum concentrations of biomarkers including IL-1ß, IL-10, IFN-γ, TNF-α and IL-6 were quantified by bead-based multiplex analysis and Serum concentration of IL-8 and IL-32 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, among the blood parameters, neutrophil and lymphocyte counts were significantly lower in severe COVID-19 patients than in the other, on the contrary, CRP was significantly higher in severe patients than in other groups. The cytokines that best distinguished controls from COVID-19 patients were IL-8 and IL-32, while IL-6 resulted the better variables for discriminate severe group. The best model performance for severe group was obtained by the combination of IL-32, IL-6, IFN-γ, and CRP serum concentration showing an AUC = 0.83. A cut off of 15 pg/ml of IL-6 greatly discriminate survivor from death patients. New insights related to the cytokine storm in COVID-19 patients, highlighting different severity of disease infection.


Assuntos
COVID-19/sangue , Citocinas/sangue , Interleucina-8/sangue , Interleucinas/sangue , Pulmão/imunologia , Idoso , Biomarcadores/sangue , COVID-19/imunologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/imunologia , Citocinas/imunologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-8/imunologia , Interleucinas/imunologia , Contagem de Linfócitos/métodos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Estudos Prospectivos , SARS-CoV-2/imunologia
15.
Eur J Clin Pharmacol ; 78(3): 339-349, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34708271

RESUMO

OBJECTIVE: To conduct a systematic review and meta-analysis of the effects of antidepressant drug therapy (with or without physical exercise) on peripheral inflammatory markers in patients with major depressive disorder (MDD). METHODS: MEDLINE, PyscINFO, Embase, and Google Scholar databases were searched until May 2020. Randomized trials that measured at least one inflammatory biomarker and included adult outpatients with MDD under antidepressant drug therapy (any drug) with or without physical exercise (any modality) were eligible. Results were summarized using the standardized mean difference (SMD) with 95% confidence intervals (95% CI) under a random-effects model. The Cochrane risk of bias tool (2010) was used to evaluate the risk of bias in the included trials. RESULTS: Sixty-three trials were identified, encompassing data from 3482 patients, and 20 investigated biomarkers. Trials had biases across multiple domains, rising concerns primarily to selection bias/performance bias/detection bias/attrition bias. SMDs between pre- and post-results indicated a significant reduction in the levels of IL-2 (SMD, - 0.25; 95% CI, - 0.41 to - 0.09, P = 0.002), IL-6 (SMD, - 0.19; 95% CI, - 0.35 to - 0.025, P = 0.024), IL-10 (SMD, - 0.32; 95% CI, - 0.57 to - 0.07, P = 0.011), and serum cortisol (SMD, - 0.35; 95% CI, - 0.58 to - 0.12, P = 0.002). Evidence supporting the influence of physical exercise combined with antidepressant drugs on peripheral inflammatory markers in MDD is sparse and heterogeneous. CONCLUSION: There is some evidence that antidepressant drug therapy is associated with an overall positive reduction in inflammatory markers, but the evidence is heterogeneous. Further research linking how inflammatory biomarkers modulate physiology related to antidepressant response is required. TRIAL REGISTRATION: CRD42020220735.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/terapia , Exercício Físico , Mediadores da Inflamação/sangue , Adulto , Antidepressivos/efeitos adversos , Biomarcadores , Proteína C-Reativa/análise , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Interferon gama/sangue , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/sangue
16.
Hepatology ; 75(3): 690-708, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34689344

RESUMO

BACKGROUND AND AIMS: Classical CD8 T cells are implicated for protective and pathogenic roles in chronic hepatitis B (CHB) infection. Recently, a subset of CD8 T cells expressing C-X-C chemokine receptor type 5 (CXCR5) and exhibiting features of TFH cells has been identified during chronic viral infections. However, in CHB, knowledge of their roles is limited. APPROACH AND RESULTS: We characterized circulating CD8+ CXCR5+/- cells and investigated their association with clinical and viral factors. We found that CHB infection did not influence the overall frequencies of CD8+ CXCR5+ cells whereas CD8+ CXCR5- cells were increased. However, among CHB, CD8+ CXCR5+ cells were higher in patients with low HBsAg and HBV-DNA levels, patients who were HBeAg negative and had high fibrosis scores, and these cells exhibited a significant association with HBsAg and HBV-DNA reduction. Contrarily, CD8+ CXCR5- cells were expanded and positively correlated with patients having high HBsAg, HBV-DNA, and alanine aminotransferase levels. CD8+ CXCR5+ cells express costimulatory molecules ICOS, OX40, CD40 ligand, inhibitory molecule programmed death 1, transcription factors B-cell lymphoma (BCL)-2, BCL-6, and signal transducer and activator of transcription 3, and are enriched in effector and central memory phenotype. Moreover, these cells are heterogeneous in nature given that they constitute different subsets of cytotoxic follicular T cells (TCF), including TCF1, TCF2, TCF17, and TCF22. Despite expressing high PD-1, CD8+ CXCR5+ cells are activated, proliferating, secreting more IFN-γ, IL-21, and IL-22, and have better cytolytic potential than CD8+ CXCR5- cells, which were inhibited after PD-1/PD-L1 blockade. CD8+ CXCR5+ cells are efficient in helping B cells in terms of plasmablasts and plasma cell generation. CONCLUSIONS: In conclusion, CD8+ CXCR5+ cells are enriched in effector phenotypes, produce HBV-specific cytokines despite increased PD-1, and are associated with HBsAg and HBV-DNA reduction. These cells competently support B-cell function, required for viral clearance, which may serve as potential therapeutic targets for CHB.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Hepatite B Crônica , Receptor de Morte Celular Programada 1/metabolismo , Receptores CXCR5/análise , Adulto , Alanina Transaminase/sangue , DNA Viral/isolamento & purificação , Feminino , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Humanos , Memória Imunológica , Interleucinas/sangue , Masculino , Subpopulações de Linfócitos T/imunologia
17.
J Allergy Clin Immunol ; 149(3): 912-922, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34688775

RESUMO

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is an acute, febrile, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated syndrome, often with cardiohemodynamic dysfunction. Insight into mechanism of disease is still incomplete. OBJECTIVE: Our objective was to analyze immunologic features of MIS-C patients compared to febrile controls (FC). METHODS: MIS-C patients were defined by narrow criteria, including having evidence of cardiohemodynamic involvement and no macrophage activation syndrome. Samples were collected from 8 completely treatment-naive patients with MIS-C (SARS-CoV-2 serology positive), 3 patients with unclassified MIS-C-like disease (serology negative), 14 FC, and 5 MIS-C recovery (RCV). Three healthy controls (HCs) were used for comparisons of normal range. Using spectral flow cytometry, we assessed 36 parameters in antigen-presenting cells (APCs) and 29 in T cells. We used biaxial analysis and uniform manifold approximation and projection (UMAP). RESULTS: Significant elevations in cytokines including CXCL9, M-CSF, and IL-27 were found in MIS-C compared to FC. Classic monocytes and type 2 dendritic cells (DCs) were downregulated (decreased CD86, HLA-DR) versus HCs; however, type 1 DCs (CD11c+CD141+CLEC9A+) were highly activated in MIS-C patients versus FC, expressing higher levels of CD86, CD275, and atypical conventional DC markers such as CD64, CD115, and CX3CR1. CD169 and CD38 were upregulated in multiple monocyte subtypes. CD56dim/CD57-/KLRGhi/CD161+/CD38- natural killer (NK) cells were a unique subset in MIS-C versus FC without macrophage activation syndrome. CONCLUSION: Orchestrated by complex cytokine signaling, type 1 DC activation and NK dysregulation are key features in the pathophysiology of MIS-C. NK cell findings may suggest a relationship with macrophage activation syndrome, while type 1 DC upregulation implies a role for antigen cross-presentation.


Assuntos
COVID-19/complicações , Células Dendríticas/imunologia , Células Dendríticas/virologia , SARS-CoV-2/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/virologia , ADP-Ribosil Ciclase 1/sangue , Adolescente , Antígenos Virais/imunologia , COVID-19/imunologia , COVID-19/virologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Apresentação Cruzada , Citocinas/sangue , Células Dendríticas/classificação , Feminino , Antígenos HLA-DR/sangue , Humanos , Imunofenotipagem , Interferon gama/sangue , Interleucinas/sangue , Células Matadoras Naturais/imunologia , Masculino , Glicoproteínas de Membrana/sangue , Modelos Imunológicos , Monócitos/imunologia , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/sangue , Linfócitos T/imunologia , Linfócitos T/virologia , Regulação para Cima
18.
Shock ; 57(1): 151-159, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34482320

RESUMO

ABSTRACT: Despite the known deleterious effects of obesity, clinical data indicate that overweight or obese patients experience higher rates of sepsis survival compared to normal and underweight patients; a phenomenon called the obesity paradox. Results from preclinical sepsis studies have not been able to replicate these findings. The objective of this study was to test the existence of the obesity paradox in a murine model of cecal slurry (CS)-induced sepsis with insulin-resistant diet-induced obese mice. Male C57BL/6 mice were provided high-fat (HFD) or low-fat (LFD) diets for 20 weeks. HFD-fed mice experienced higher rates of survival compared to LFD-fed mice after septic challenge induced by CS injection (66% vs. 25%, P = 0.01, survival assessed for 14 days). Despite the survival advantage, HFD-fed mice had higher rates of positive bacterial cultures and increased markers of kidney injury. Circulating levels of IL-6, IL-1ß, TNFα, and IL-23 were equivalent 24 h after CS-injection; however, IL-17A was uniquely increased in HFD-fed mice. While LFD-fed mice maintained euglycemia, HFD-fed mice were hyperglycemic 6 and 12 h after CS-injection. Stable isotope resolved metabolomics analysis of liver tissue showed diverging pathways of glucose utilization during sepsis, with LFD-fed mice significantly upregulating glycolytic activity and HFD-fed mice decreasing glucose entry into the TCA cycle. This murine study corroborates clinical data that obesity confers a survival benefit in sepsis, albeit at the expense of more significant organ injury. The mechanisms promoting survival in the obese remain unknown; however, this model appears to be well-poised to begin answering this question. Differences in glucose utilization are a novel target to investigate this paradox.


Assuntos
Camundongos Obesos , Sepse/mortalidade , Injúria Renal Aguda/sangue , Animais , Citocinas/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Interleucinas/sangue , Camundongos Endogâmicos C57BL , Sepse/sangue , Fator de Necrose Tumoral alfa/sangue
19.
Int J Rheum Dis ; 25(1): 56-60, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34806316

RESUMO

OBJECTIVE: There is an unmet need for a reliable biomarker for the differentiation of axial spondyloarthritis (AxSpA) from its mimickers. Serum levels of interleukin-22 (IL-22) have previously been found to be significantly elevated in patients with AxSpA compared with healthy individuals or persons with osteoarthritis. METHODS: Consecutive patients with established or suspected AxSpA were enrolled. The clinical data, as well as results of laboratory and imaging studies, were acquired from patients' charts. The final diagnosis of definite or probable SpA, or an alternative diagnosis, was determined, and the serum levels of IL-22 were examined by enzyme-linked immunosorbent immunoassay. RESULTS: Interleukin-22 levels were significantly higher in patients with definite AxSpA (29 patients) compared with patients with alternative diagnoses (14 patients) and healthy volunteers (16 individuals; P < 0.001 for both comparisons). The sensitivity and specificity of the serum IL-22 for the AxSpA diagnosis were 0.68 (95% CI 0.49-0.84) and 0.86 (95% CI 0.68-0.95), respectively, for the cut-off value of 5 pg/mL. In patients with AxSpA, serum IL-22 levels did not correlate with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), or serum C-reactive protein. CONCLUSION: Serum IL-22 levels are elevated in patients with the clinical diagnosis of AxSpA and can potentially serve as an independent biomarker for the differentiation of AxSpA from its non-inflammatory mimickers.


Assuntos
/sangue , Interleucinas/sangue , Adulto , Idoso , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
20.
Int J Lab Hematol ; 44(1): 150-156, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34528397

RESUMO

INTRODUCTION: Accumulating evidence has indicated that interleukin (IL)-27 and its gene polymorphisms exert pivotal impact on several autoimmune disorders. This research intended to investigate the relationship between IL-27 rs153109 polymorphism with risk and prognosis for aplastic anemia. METHODS: IL-27 rs153109 polymorphism was detected with polymerase chain reaction-ligase detection reaction in 238 patients with aplastic anemia and 215 normal individuals. Enzyme-linked immunosorbent assays were applied to measure the plasma level of IL-27. RESULTS: Frequencies of rs153109 AA and GG genotype were statistically higher in aplastic anemia patients compared to controls. Similar results were observed when further divided patients into nonsevere and severe ones. That means carriers of AA and GG genotype are accompanied by an increased risk of developing aplastic anemia. Plasma IL-27 levels of aplastic anemia patients were remarkably elevated than normal group and had positive relation with disease severity. Furthermore, patients with AA genotype had obviously higher IL-27 levels than ones with AG and GG genotype. Moreover, patients carrying AA genotype exhibited a poorer reaction to immunosuppressive therapy and were more prone to clonal evolution. CONCLUSION: IL-27 rs153109 polymorphism confers genetic predisposition to aplastic anemia and influences disease prognosis, potentially by regulating IL-27 expression, which help broaden potential pathogenesis of aplastic anemia. Specifically, for patients with AA genotype, more aggressive therapeutic strategies such as hematopoietic stem cells transplantation are warranted.


Assuntos
Alelos , Anemia Aplástica/epidemiologia , Anemia Aplástica/genética , Predisposição Genética para Doença , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Anemia Aplástica/diagnóstico , Biomarcadores , Estudos de Casos e Controles , China/epidemiologia , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Interleucinas/sangue , Estimativa de Kaplan-Meier , Vigilância da População , Prognóstico , Índice de Gravidade de Doença
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