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.
Martín
J
J
Department of Hepatology, Fundación Jiménez Díaz, Madrid, Spain.
de Sequera
P
P
Quiroga
J A
JA
Rico
M
M
Fernández
M
M
Arocena
C
C
Caramelo
C
C
Carreño
V
V
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