Plasma IL-17A levels in patients with late-life depression

Objective: A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD. Methods: A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments. Results: Plasma IL-17A levels were not statistically different between LLD patients and controls (p = 0.94). Among all subjects (LLD + control), plasma IL-17A did not correlate significantly with depressive symptoms (rho = -0.009, p = 0.92) but a significant correlation was observed with cognitive assessments (rho = 0.22, p = 0.01). Conclusion: Our findings do not support an association between plasma IL-17A levels and LLD. Nevertheless, IL-17A may be associated with cognitive impairment in LLD patients. If this finding is confirmed in future longitudinal studies, modulation of the T-helper 17 cell (Th17) immune response may be a treatment target for cognitive impairment in this population.

The potential role of Th17 lymphocytes in patients with psoriasis

Abstract: Background: Psoriasis is a chronic inflammatory disorder, characterized by increased keratinocyte proliferation due to abnormal differentiation of basal keratinocytes. The etiology of the disease is unclear, and according to the survey results, it is hypothesized that a combination of genetic and environmental factors prompts an abnormal immune response in patients with psoriasis. CD4+ Th cells play a multifaceted role in both immune defense and pathogenesis of certain diseases such as psoriasis. Nonetheless, the exact contribution of different subpopulations of Th cells in psoriasis is still not clear. Objective: The aim of present study was to determine the mRNA expression level of RORC as potential inducer of Th17 cell differentiation and expression pattern of Th17-signature cytokines (IL-17A and IL-22). Methods: Twenty patients with psoriasis and twenty-one healthy subjects were included in the study. Peripheral blood mononuclear cells (PBMCs) were separated and expression of three genes were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR). Plasma levels of IL-17 and IL-22 were also evaluated by ELISA. Results: RORC, IL-17A and IL-22 gene expression was significantly higher in patients with psoriasis compared with healthy controls (P<0.05). In addition, a marked increase in plasma IL-17A and IL-22 levels was observed in patient group compared to controls (P<0.001). Study limitations: small number of patients. Conclusion: These data suggest that Th17 response may contribute to the pathogenesis of psoriasis.

Imbalance of Th17 and Treg in peripheral blood mononuclear cells of active tuberculosis patients

Abstract Objective: Maintaining a right balance between Th17 and Treg might be critical to the immunopathogenesis of active tuberculosis (TB). This study aimed to assess whether the Th17/Treg balance is altered in active TB patients. Methods: 250 study subjects (90 active TB patients, 80 latent TB subjects, and 80 healthy controls) were recruited for the study. The expression of Th17 and Treg in peripheral blood mononuclear cells (PBMCs) in the 250 subjects was investigated by flow cytometry. Plasma levels of cytokines IL-17 and IL-10, which are related to Th17 and Treg, respectively, were determined by ELISA. Results: The percentages of Th17 and Treg in PBMCs from active TB patients were significantly higher than those from latent TB or control groups (Th17: 4.31 ± 1.35% vs. 1.58 ± 0.71% or 1.15 ± 0.49%, p < 0.05; Treg: 11.44 ± 2.69% vs. 7.54 ± 1.56% or 4.10 ± 0.99%, p < 0.05). The expression of IL-17 and IL-10 was significantly increased in active TB patients in comparison to that in latent TB or control groups (IL-17: 16.85 ± 9.68 vs. 7.23 ± 5.19 or 8.21 ± 5.51 pg/mL, p < 0.05; IL-10: 28.70 ± 11.27 vs. 20.25 ± 8.57 or 13.94 ± 9.00 pg/mL, p < 0.05). Conclusions: Our study demonstrated an altered balance of Treg/Th17 in active TB patients, with higher percentages of Th17 and Treg in PBMCs. Further research on this imbalance may offer a new direction for TB treatment.

Elevated IL-17 and TGF-beta serum levels: a positive correlation between T-helper 17 cell-related pro-inflammatory responses with major depressive disorder

Introduction: Depression is a mental disorder that highly associated with immune system. Therefore, this study compares the serum concentrations of IL-21, IL-17, and transforming growth factor beta [TGF-beta] between patients with major depressive disorder and healthy controls

Methods: Blood samples were collected from 41 patients with major depressive disorder and 40 healthy age-matched controls with no history of malignancies or autoimmune disorders. The subjects were interviewed face to face according to DSM-IV diagnostic criteria. Depression score was measured using completed Beck Depression Inventory in both groups. The serum concentrations of IL-21, IL-17, and TGF-beta were assessed using ELISA

Results: The mean score of Beck Depression score in the patient and control groups was 35.4 +/- 5.5 and 11.1 +/- 2.3. IL-17 serum concentrations in the patients and the control group were 10.03 +/- 0.6 and 7.6 +/- 0.6 pg/mL, respectively [P=0.0002]. TGF-beta level in the patients group was significantly higher than compare to the control group; 336.7 +/- 20.19 vs. 174.8 +/- 27.20 pg/mL, [P<0.0001]. However, the level of IL-21 was not statistically different between the two groups 84.30 +/- 4.57 vs. 84.12 +/- 4.15 pg/mL [P>0.05]

Conclusion: Considering pro-inflammatory cytokines, current results support the association of inflammatory response and depressive disorder. So, it seems that pro-inflammatory factors profile can be used as indicator in following of depression progress and its treatment impacts

Interleukin 17 A, hepatosplenic mansonic schistosomiasis and atherosclerosis / Interleucina 17 A, esquistossomose mansônica forma hepatoesplênica e aterosclerose

Objective: To evaluate serum concentrations of interleukin 17A (IL17A) in mansonic schistosomiasis patients, while the secondary objectives were to detect atherosclerotic disease, and to evaluate serum concentrations of interleukin 22 (IL22). Methods: This study included 30 patients with an established diagnosis of hepatosplenic mansonic schistosomiasis and 10 healthy volunteers. Comparative analyses of IL17A and IL22 concentrations were performed on the sera of patients and controls. Atherosclerosis was evaluated through carotid artery intima-media thickness measurement of the first 15 patients enrolled. Results: There were no differences in IL17 A concentrations (15.63±0.00pg/mL vs. 15.63±0.00pg/mL; p=1) and in IL22 concentrations (7.81±0.00pg/mL vs. 7.81±0.00pg/ mL, p=1) between patients and controls. The overall mean of intima-media thickness was 0.7±0.2mm. Conclusions: Serum concentrations of IL17A and IL22 were equal between patients and controls (undetectable or low concentrations). No patients had atheroma.

Objetivo: Avaliar as concentrações séricas de interleucina 17A (IL17A) em pacientes com esquistossomose mansônica, enquanto os objetivos secundários foram detectar a doença aterosclerótica e avaliar as concentrações séricas de interleucina 22 (IL22). Métodos: Este estudo incluiu 30 pacientes com diagnóstico estabelecido de esquistossomose mansônica em sua forma hepatoesplênica e 10 voluntários saudáveis. Análises comparativas de concentrações de IL17A e IL22 foram realizadas em soros de pacientes e controles. A aterosclerose foi avaliada pela medida do complexo íntima-média dos primeiros 15 pacientes recrutados. Resultados: Não houve diferença nas concentrações de IL17A (15,63±0,00pg/mL vs. 15,63±0,00pg/mL; p=1) e nas concentrações IL 2 (7,81±0,00pg/mL vs. 7,81±0,00pg/mL; p=1) entre os pacientes e controles. A média geral da espessura da camada média da íntima foi de 0,7±0,2mm. Conclusões: As concentrações séricas de IL17A e IL22 foram iguais entre pacientes e controles (concentrações indetectáveis ou baixa). Nenhum dos pacientes apresentou ateroma.

IL-17 assay in adult T-cell leukemia/lymphoma patients with dermatophytosis

Assess IL-17 level as proinflamtory cytokine and predictor for the outcome of inflammatory process in ATLL patients with dermatophytosis. Isolation and identification of different types of dermatophytes infecting patients with ATLL. 58 subjects were included in this study [16 adult patients with adult T-cell leukemia / lymphomaclinically diagnosed to have dermatophytosis, 14 adult patients with adult T-cell leukemia / lymphoma clinically diagnosed to have no dermatophytosis, 12 age and sex matched patients clinically diagnosed to have dermatophytosis and 16 Age and sex matched apparently healthy Controls]. Sampleswere examined microscopically using 20% KOH and cultured on into SDA containing chloramphenicol [0.5%] with/without cycloheximide [0.5%] and Dermatophyte test medium [DTM]. in the non-ATLL patients with dermatophytosis, the serum IL-17 level was significantly increased compared with the healthy controls. In ATLL patients either with or without dermatophytosis, the IL-17 levels were significantly lower than those in the healthy controls. There was no significant difference in the IL-17 level between ATLL patients with dermatophytosis and those without dermatophytosis. Again, it is suggested that ATLL patients have low levels of IL-17, which cannot be enhanced by the presence of dermatophytosis. Among patients with ATLL with dermatophytosis [Group I] T. rubrum was the commonest dermatophyte causing infection; 64% of samples [tineacorporis 46%, tineaunguium 18%], whereas T. mentagrophytes was the 2[nd] commonest dermatophyte; 27% [tineaunguium 27%], lastly T. tonsurans; 9% [tineacorporis 9%]. In patients with Non-ATLL with dermatophytosis [Group III] T. rubrum was also the commonest dermatophyte causing infection; 64% of samples [tineacorporis 7%, tineaunguium 14%, tineapedis 43%], whereas T. mentagrophytes was the 2nd commonest dermatophyte; 29% [tineaunguium 7%, tineapedis 22%], lastly T. tonsurans; 7% [tineacorporis 7%]. Our data provides clinical evidence linking Th17 cells to immune deficiency in ATLL and opens a new avenue in the study of tumor immunotherapy based on promoting Th17 cell population

Negative association of serum IL-6 and IL-17 with type-II diabetes retinopathy

Diabetes mellitus [DM] is a health concern which leads to complications such as retinopathy. Pakistan has 6.9 million people living with DM and this toll will be doubled by 2025. To determine serum IL-6 and IL-17 of type 2 diabetes mellitus [T2DM] patients with retinopathy. In this cross-sectional case- control study, 212 subjects enrolled which were categorized into 3 groups. Group-I included 30 subjects without diabetes, group-II consisted of 30 subjects with T2DM without retinopathy and group-III consisted of 152 subjects with T2DM and retinopathy. Serum IL-6 and IL-17 levels were determined by ELISA. Data was analysed using SPSS 17.0 and one way ANOVA to observe group mean differences. Longer mean duration of disease was detected in group-III than group-II [p=0.007]. Highest IL-6 level was detected in group-II and highest IL-17 level was detected in group-I. For IL-6, significant differences were detected among groups in total, between Group-I and Group-III and between Group-II and Group-III [p<0.0001 each]. Regarding IL-17, significant differences were found among groups in total [p=0.002] and between Group-I and Group-III [p=0.001]. No significant difference in the percentages of HbA1c observed between groups. Age, gender and duration of diabetes contribute to T2DM retinopathy. Serum IL-6 and IL-17 were inversely associated with T2DM retinopathy

Estimation of serum level of interleukin-17 and interleukin-4 in leprosy, towards more understanding of leprosy immunopathogenesis.

Background: Combating Mycobacterium leprae is known to be via T-helper1 response. However, other T-helper effector cells; T-helper17 and T-helper2; play a role, particularly in the context of disease type. Aims: We aimed to evaluate serum levels of interleukin (IL)-17 (T-helper17 cytokine) and IL-4 (T-helper2 cytokine) in untreated patients with different types of leprosy, compared to controls. Methods: Using enzyme-linked immunosorbent assay, serum IL-17 and IL-4 levels were estimated in 43 leprotic patients and 43 controls. Patients were divided into six groups; tuberculoid, borderline cases, lepromatous, erythema nodosum leprosum (ENL), type 1 reactional leprosy, and pure neural leprosy. Patients were also categorized according to bacillary load and the presence or absence of reactions. Results: Serum IL-17 was signifi cantly lower in cases (4-61.5 pg/mL; median 19), compared to controls (26-55 pg/mL; median 36) (P < 0.001), and was signifi cantly lower in each type of leprosy compared to controls, with the lowest level in lepromatous leprosy (4-61.5 pg/mL; median 12.5). Signifi cantly elevated serum IL-4 was found in patients (1.31-122.4 pg/mL; median 2.31) compared to controls (1.45-5.72 pg/mL; median 2.02) (P = 0.008), with the highest level among lepromatous leprosy patients (2-87.2 pg/mL; median 28.9), and the lowest in type 1 reactional leprosy (1.4-2.5 pg/mL; median 1.87) (P = 0.006). Conclusion: Defective secretion of IL-17 is related to disease acquisition as well as progression toward lepromatous pole in leprosy patients. The overproduction of IL-4 in patients with lepromatous leprosy may infer their liability to develop ENL. Nevertheless, the small number of the studied population is a limitation.

Serum interleukin-17 & nitric oxide levels in patients with primary Sjögren's syndrome.

Background & objectives: The interleukin (IL)-17 producing T-helper cells have been linked to pathogenesis of autoimmunity and mostly investigated in rheumatoid arthritis (RA). In this study we tested the IL-17 levels, as well as the levels of nitric oxide (NO) as possible IL-17-induced product, in patients with primary Sjögren's syndrome (pSS), an intricate and complex chronic autoimmune disorder of exocrine glands. Methods: Serum IL-17 levels and nitrite concentrations determined in patients with pSS (n=30) were compared with the values obtained in patients with RA (n=10) and healthy controls (n=15). The values obtained for IL-17 in pSS patients were also associated with the patients’ clinical characteristics, particularly the rheumatoid factor (RF) and total antinuclear antibodies (tANA) levels. Results: Serum concentrations of IL-17 were significantly (P<0.01) higher in patients with pSS (12.9 ± 28.0 pg/ml) as compared to those obtained in healthy individuals (0.2 ± 0.6 pg/ml), but not as high as the values obtained for the patients with RA (34.5 ± 56.2 pg/ml). The mean IL-17 levels were significantly (P<0.05) higher in the pSS patients positive for rheumatoid factor (20.3 ± 33.3 pg/ml) than in RF-negatives (0.3 ± 0.6 pg/ml). Mean serum concentrations of IL-17 were also higher in antinuclear antibody (ANA)-positive samples (19.8 ± 33.5 pg/ml) in comparison to ANA-negative sera (1.1 ± 3.1 pg/ml) (P<0.05). The NO levels also showed elevated values in both pSS and RA patients, as compared to the healthy controls, since mean nitrite levels in patients with pSS and RA were 38.2 ± 29.2 μM and 41.7 ± 21.1 μM, respectively, while those in healthy controls were significantly lower, at 19.2 ± 10.5 μM. Interpretation & conclusions: The findings of this study showed that there was increased IL-17 and NO production in patients with primary SS, especially if they had associated elevated rheumatoid factor and antinuclear antibody values.

[Evaluation of cytokines changes in patients infected with giardia lamblia in comparison with healthy subjects]

Human Giardisis infection is caused by the flagellate protozoa. Giardia lamblia, which lives in the small intestine, causing damage and may also cause gastrointestinal symptoms. This parasitic disease has a worldwide distribution and prevalence varies from 5% to 30%. The role of both humeral and cellular immune response in the host defense against parasites has proven. Since an immune response is directly affected by cytokine, study of cytokines changes in patients with giardiosis is of particular importance. In this study the serum levels of IL-2 - 4 - 6 to 17 and 23 in patients and healthy subjects were measured and compared. Fasting blood samples were taken from the volunteers, ELISA was performed to measure cytokines. In this study, the amount of IL-2 and IL-6 in infected patients was significantly more than the controls, but IL-4 levels were significantly lower in infected individuals [P=0.0001]. Also for the first time in people with giardiasis IL- 17 and IL-23 was measured and there was a significant aifference in these cytokines between the infected patients healthy controls[respectively P=0.044 and P=0.03]. Host defense response against parasitic infections, is directly and affected by cytokines. Increased interleukin 2, 6, 17 and 23 in patients with Giardiosis was probably caused by immune response and local intestinal inflammation

Interleukin-27 and its relation to disease parameters in SLE patients

IL-27 exerts profound anti-inflammatory effects in several experimental autoimmune models, suggesting that it may be therapeutically relevant in SLE. To evaluate IL-27 level in SLE patients and its association to clinical manifestations, disease activity parameters and management strategy. We studied 80 SLE patients and 50 controls in a cross sectional study. Demographic, clinical and serological data were evaluated. Systemic lupus erythematosus disease activity index [SLEDAI] and Systemic Lupus International Collaboration Clinics/ACR damage index [SLICC] were assessed. Serum IL-27 was measured by ELISA. There was statistically significant difference in IL-27 level in SLE patients and healthy controls [9.7 +/- 21.9 pg/ml vs 20.2 +/- 47.3 pg/ml in SLE vs controls, respectively] [p = 0.04], also it was found that IL-27 level was statistically significantly lower in SLE patients with lupus nephritis [p = 0.02] and cerebritis [p = 0.03]. Interleukin 27 level had a statistically significant negative correlation with the cumulative dose of hydroxychloroquine and azathioprine [r = -0.3, p = 0.03 and r = -0.3 and p = 0.04, respectively]. IL-27 has anti-inflammatory effect in SLE patients especially those without nephritis or cerebritis and can be therapeutically relevant in SLE. To confirm our results we propose larger scale, multicentre studies with longer evaluation periods

Investigating the Relationship between Serum Interleukin-17 Levels and Systemic Immune-Mediated Disease in Patients with Dry Eye Syndrome

PURPOSE: To investigate the association between dry eye syndrome (DE) and serum levels of interleukin (IL)-17 in patients with systemic immune-mediated diseases. METHODS: IL-17 and IL-23 levels were measured in the sera of patients whose tear production was <5 mm on the Schirmer test. Subjects included patients with chronic graft-versus-host disease (GVHD), rheumatoid arthritis (RA), Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), and no systemic disease. Corneal/conjunctival fluorescein staining was scored and the correlation between the score and the IL-17 level was evaluated. RESULTS: A strong correlation existed between IL-17 level and the type of systemic disease. IL-17 was significantly elevated in patients with chronic GVHD compared to those with RA and SS. IL-17 was not detectable in patients with SLE or in those without systemic disease. IL-23 was not detected in any of the subjects. IL-17 was significantly increased in patients with high fluorescein staining scores. CONCLUSIONS: Our data suggest that IL-17 is involved in the pathogenesis of DE in patients with systemic immune-mediated diseases.

longitudinal study to investigate the role of IL-6 and IL-7 in the pathologenesis of early rheumatoid arthritis

Previous researches indicate that IL-6 is a pro-inflammatory cytokine in RA that can drive Th17 cell development in mice and humans. Data from experimental arthritis models suggest that Th17 cells are pathogenic via production of the pro-inflammatory cytokines IL-17 and TNF alpha, leading to monocyte and fiboblast activation, and involvement in osteoclastogeneis and joint damage. The aim of this study is to investigate if interleukin-6 [IL-6] and/or interleukin-17 [IL-17] and Th17 cells are biomarkers for disease progression and severity in early Undifferentiated Arthritis [UA] and/Rheumatoid Arthritis [RA] patients. We performed a longitudinal study recruiting 20 patients with either undifferentiated inflammatory arthritis or early rheumatoid arthritis. We also recruited 30 age [mean = 46] and sex-matched healthy controls. The patients were assessed at baseline, 6 and 12 months for the American College of Rheumatology [ACR] criteria, Rheumatoid factor [RF], Anti Citrullinated Peptides [Anti-CCP], ESR, CRP, X-Ray of the hands and feet, joint count, patient global assessment, DAS28 and Quality of Life [HAQ] measurements. Peripheral blood and serum samples were taken and PBMC isolated. Cell subset analysis [CD3, CD4/CD8, and CD14] was performed ex vivo. Peripheral blood monocytes in RA and UDA showed the proportion of IL6 CD14+Monocytes significantly higher in RA patients at base line than the UDA. Sero-positive patients were higher in the proportion of [Total IL17 CD3 +CD4+Tcells, IFNgamma+IL17+CD3+CD4+Tcells, IL6 CD14+Monocytes] than the sero-negative patients but that differences did not reach statistical significance. The longitudinal follow up for the early arthritis group, showed a significant change in the%IL6 Monocytes. The proportion of IL6 and IL17 in peripheral blood of early rheumatoid arthritis shows a weak correlation with disease activity which could not be an ideal biomarker for disease activity in comparison to synovial level of these cytokines

Reduced interleukin-17 expression of Burkholderia pseudomallei-infected peripheral blood mononuclear cells of diabetic patients.

Burkholderia pseudomallei is the causative agent of melioidosis. One of the main risk factors for B. pseudomallei infection in endemic areas is diabetes mellitus. The present study investigated IL-17 mRNA and protein expression by peripheral blood mononuclear cells in response to B. pseudomallei infection in 10 diabetic patients in comparison to 10 healthy blood donors. The IL-17 expression in diabetic patients was significantly lower (p < 0.05) than in the controls. However, IL-23 mRNA expression of the 2 groups was comparable. The present findings suggest that melioidosis affects T cell IL-17 production and that patients with diabetes mellitus have a defective IL-17 production in response to this type of infection.

[ serum and sputum levels of Interleukin - 17 in patients with asthma]

Association of asthma with Type 2 T- helper system is well realized. Recent clinical evidence show that acute, severe exacerbations of asthma are associated with recruitment and activation of neutrophils in the airways. The lymphocytes T helper 17 [Th17] cells can probably recruit neutrophils to an inflammatory site through producing IL-17. The objective of this study was to investigate the level of interlukin-17 [IL-17] in serum and sputum of asthmatic subjects. Also, the study aimed at evaluating the correlation between concentrations of IL-17 and the frequency of inflammatory cells in the sputum of asthma at different stages. Fifty newly diagnosed asthmatics and 12 non-asthmatics healthy subjects, as the control group, entered this prospective study. None of them reported any recent history of infection and steroid usage. Then, samples from venous blood and sputum [Induced by Hypertonic saline%5] were obtained. The severity of asthma was classified according to GINA 2004 guidelines. The Concentrations of IL-17 in serum and supernatant of induced sputum were determined by ELISA method. Total serum IgE level was also determined in order to classify asthmatic subjects into allergic and non-allergic groups. As the findings of the study suggest, serum IL-17 level was significantly higher in asthmatic patients than in the normal control subjects [78.8 +/- 58.7 vs 17.7 +/- 2.4 pg/dl, P=0.025]. IL-17 was found to be significantly increased in sputum of the subjects with asthma, as compared to the control subjects [31.6=/-20.9 vs 21.5 +/- 16.6 pg/dl, P=0.012]. In addition, allergic and non-allergic asthmatic patients showed a significantly higher concentration level of serum IL-17 than the normal controls [80.8 +/- 50.3, P+0.023 and 102.7 +/- 43.6, P=0.002vs 17.7 +/- 2.4 ng/ml]. But, it was found that the levels of both serum and sputum IL-17 in the allergic asthma group were not significantly higher than those in the non-allergic asthmatics. Moreover, serum IgE level was significantly higher in allergic asthmatic patients than non-allergic asthmatic and normal control subjects [295.8=/-168 vs. 99.1 +/- 90.0 P=0.001 and 49.7 +/- 41.8, P=0.001]. The results further revealed that macrophage was decreased in sputum but neutrophil and eosinophil were significantly increased. However, the increase of IL-17 was not correlated with asthma severity. Besides, there was no significant difference between allergic and non-allergic asthmatic subjects, in terms of IL-17. We propose that IL-17 may play a role in the airway inflammation of asthmatics by recruiting neutrophils into the lung, no matter if they are suffering from allergic or non-allergic asthma