Serum levels of Th17 associated cytokines in chronic hepatitis C virus infection.

The Th17-mediated immune response was investigated in patients chronically infected with hepatitis C virus (HCV) by determining the serum levels of the cytokines involved in the induction of the Th17 response (TGF-ß and IL-6), the cytokines produced by Th17 cells (IL-17A, IL-17F and IL-22) and the cytokines whose production is stimulated by Th17 lymphocytes (IL-8 and GM-CSF). We investigated the relationships among the levels of these cytokines by assessing clinical findings, liver histology and viremia. Sixty untreated patients and 28 healthy individuals were included in the study. Cytokine levels were determined using ELISA. Differences between HCV and control groups were identified in the median levels of IL-17F (controls=172.4 pg/mL; HCV=96.8 pg/mL, p<0.001) and IL-8 (controls=30.1 pg/mL; HCV=18.1 pg/mL, p<0.05). IL-6 levels were higher in patients presenting moderate liver necroinflammation than in patients with mild or no liver necroinflammation (p<0.05). IL-17F levels were increased in patients that had increased ALT levels. Additionally, a strong positive correlation was observed between IL-17F and IL-22 levels in the two groups investigated, and the IL-17F/IL-22 ratio was lower in the patients infected with HCV (p<0.0001). Patients with low HCV viral loads had higher median levels of IL-8 (32.5 pg/mL) than did patients with high HCV loads (16.7 pg/mL, p<0.05). These results suggest that in chronic hepatitis C infection, IL-17F and IL-8 could be associated with the control of liver injury and infection, respectively.

Serum cytokine profile in hepatitis C virus carriers presenting cryoglobulinaemia and non-organ-specific autoantibodies.

This work investigated the serum cytokine profile (IL-2, IL-4, IL-5, IL-10, IFN-gamma and BAFF) of hepatitis C virus (HCV) carriers with autoimmunity. Forty-seven HCV carriers and 28 healthy controls were evaluated. Cytokine levels were measured by ELISA. Patients and controls presented similar levels of IL-2, IL-4, IL-5, IL-10, IFN-gamma and BAFF (p>0.05). Cryoglobulinaemic HCV carriers had increased IL-2 (p=0.013), IL-5 (p=0.018) and BAFF (p=0.050). IFN-gamma level was decreased in HCV carriers with rheumatoid factor in comparison with those that were RF-seronegative (p=0.035). Patients with beta2GPI IgA antibodies when were compared with those without this autoantibody, had more serum IL-2 (p=0.009), IL-5 (p=0.018) and BAFF (p=0.039). Interleukin-2 was increased in HCV carriers with positive ANA when they were compared with ANA-seronegative carriers (p=0.044). Interleukins IL-4 and IL-10 were not associated with autoimmunity (P>0.05). In HCV carriers, IL-2 was correlated with IL-5 (p<0.0001) and IFN-gamma (p=0.015), and IL-5 with IFN-gamma (p=0.015). We concluded that the serum profile of cytokines in HCV carriers presenting autoimmune markers may be mainly represented by increased IL-2, IL-5 and BAFF.

Autoimmunity in hepatitis C virus carriers: involvement of ferritin and prolactin.

BACKGROUND: Ferritin and prolactin have been associated with active autoimmune diseases as systemic lupus erythematosus and autoantibody production, but have been little studied in viral infections that present autoimmunity. OBJECTIVE: To investigate the association of these two autoimmune mediators with the presence of cryoglobulinaemia and non-organ-specific autoantibodies (RF, SMA, ß2GPI IgA antibody and ANA) in Brazilian individuals chronically infected with hepatitis C virus (HCV). METHODS: Ninety-nine patients were evaluated. Ferritin and prolactin levels were determined by chemiluminescent immunoassays. RESULTS: Hyperprolactinemia was found in 10 (six men and four women) out of 99 (10.1%) hepatitis C patients. Thirty-eight out of 99 (38.4%) HCV carriers had hyperferritinemia (median level 385ng/mL). Neither hyperprolactinemia nor hyperferritinemia was associated with cryoglobulinaemia or non-organ-specific autoantibodies (p>.05). There was an association between hyperprolactinemia and the infection with HCV genotype 3 (p<.01). Ferritin and ALT levels were correlated (p<.05). CONCLUSION: Our results suggest that neither prolactin nor ferritin is involved with the extra-hepatic manifestation of autoimmunity observed in HCV carriers.