The pathogenic role of immune-mediated mechanisms in chronic hepatitis C virus (HCV) infection has not yet been elucidated. In this study, we report different cytokine expression profiles from hemodialysis (HD) and non-HD HCV (+) patients. IL-1beta, IL-2, IL-4, IL-6, TNF-alpha, and TGF-beta1 serum levels, and liver biochemical parameters were determined in 85 individuals (41 HD patients and 44 non-HD patients). Screening for HCV RNA and anti-HCV antibodies was performed using qualitative and quantitative reverse transcription polymerase chain reaction (RTPCR), and standardized enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) methods, respectively. IL-4 and IL-1beta demonstrated decreased serum levels in non-HID HCV carriers compared with healthy controls. Both T helper (Th) 1 and Th2 lymphocytes were highly associated with chronic HCV infection, as indicated by the increased IL-2, IL-4, and IL-6 cytokine circulating levels in all chronic active hepatitis (CAH) patients examined. An enhanced Th2 response (IL-4 and IL-6) coupled with increased TNF-alpha and IL-1beta serum levels was reported in HID HCV (-) patients. In conclusion, our data show that a virus-induced Th2 and IL-1beta immunosuppression is an early event in HCV-related chronicity. Long-term HD specifically exerts a chronic effect on IL-6, IL-1beta, and TNF-alpha serum circulating levels. Irrespective of the HID status, HCV viremia, and liver biochemistry parameters, both Th1 and Th2 responses are highly associated with chronic HCV infection. (C) 2002 Wiley-Liss, Inc.