Cytokines modulate general and
virus infection-related host immune responses. We have investigated
cytokine responses in
chronic renal disease patients with regard to haemodialysis and hepatitis C virus (HCV)
infection. Compared with healthy subjects with normal renal function (n=15), non-dialyzed/renal disease individuals without HCV
infection (n=11) showed increased production of tumour
necrosis factor (
TNF)-alpha,
interleukin (IL-)6,
IL-10,
interferon (IFN-)gamma and
IL-12 by blood mononuclear cells (P<0.05). These inflammatory
cytokine responses were abolished in haemodialysis patients (n=37;P<0.05), except for
IL-12. This hyporesponsiveness in haemodialysis patients 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=24) or without (n=13) HCV
infection. However, HCV-positive haemodialysis patients 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 hepatitis C patients without renal disease (n=25). On the contrary,
IL-10 stimulation was higher in HCV-positive haemodialysis patients (P<0.01). These results disclose the presence in haemodialysis patients of markedly abnormal general and HCV
infection-related
cytokine responses; the inhibitory alterations appear to affect predominantly the stimulated responses via the Th(1)subset and its relationship with monocyte response with possible pathogenic and therapeutic implications.