Role of haemodialysis and hepatitis C virus infection in spontaneous and induced cytokine production of patients with chronic renal disease

Cytokines modulate general and virus infection-related host immune response s. We have investigated cytokine responses in chronic renal disease patient s with regard to haemodialysis and hepatitis C virus HCV) infection. Compar ed with healthy subjects with normal renal function (n=15), non-dialyzed/re nal disease individuals without HCV infection (n=11) showed increased produ ction of tumour necrosis factor (TNF)-alpha, interleukin (IL-)6, IL-10, int erferon (IFN-)gamma and IL-12 by blood mononuclear cells (P<0.05). These in flammatory cytokine responses were abolished in haemodialysis patients (n=3 7; P<0.05), except for IL-12, This hyporesponsiveness in haemodialysis pati ents was more evident in stimulatory conditions, as shown by the consistent inhibition of IFN-gamma production, and the failure of exogenous IFN-gamma to prime for IL-12 inducibility (P<0.01). The disturbed cytokine response appeared to focus in the T-helper lymphocyte phenotype 1 (Th-1) because the stimulation of IL-6 and IL-10 (Th-2 phenotype cytokines) was not impaired. The pattern of response was similar among haemodialysis patients with (n=2 4) or without (n=13) HCV infection. However, HCV-positive haemodialysis pat ients had a blunted TNF-alpha response (P<0.05) and failed to increase the stimulated IFN-gamma and IL-12 production (P<0.01) compared with chronic he patitis C patients without renal disease (n=25), On the contrary, IL-10 sti mulation was higher in HCV-positive haemodialysis patients (P<0.01). These results disclose the presence in haemodialysis patients of markedly abnorma l general and HCV infection-related cytokine responses; the inhibitory alte rations appear to affect predominantly the stimulated responses via the Th- 1 subset and its relationship with monocyte response with possible pathogen ic and therapeutic implications. (C) 2000 Academic Press.