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 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.
Department of Hepatology, Fundación Jiménez Díaz, Madrid, Spain.
J
J
Martín
P
P
de Sequera
J A
JA
Quiroga
M
M
Rico
M
M
Fernández
C
C
Arocena
C
C
Caramelo
V
V
Carreño
D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D008297:Male; D006435:Renal Dialysis; D014511:Uremia / Q000209:etiology / Q000378:metabolism
D016207:Cytokines