Intrahepatic cytokine profile in renal-transplant patients infected by hepatitis C virus.
In order to examine the immunopathogenesis of hepatitis C virus (HCV)-related liver injury in renal-transplant patients, intra-hepatic cytokine profiles were examined in 38 liver biopsies from 38 patients by measuring messenger RNA (mRNA) concentrations by a real-time PCR method of a Th1 cytokine (i.e., interferon (IFN)-gamma), a Th2 cytokines (i.e., interleukine (IL)-10), a proinflammatory cytokine (i.e., IL-8), and a potent fibrogenic factor (transforming growth factor [TGF]-beta). There was no significant difference in TGF-beta, IFN-gamma, IL-10, or IL-8 levels of expression according to liver-activity grade, liver-fibrosis stage, the concentration of HCV RNA at liver biopsies, or the HCV genotype. However, IFN-gamma/beta-actin mRNA concentration was higher than the IL-10/beta-actin mRNA concentration in patients with F3 Metavir score. Median IFN-gamma/beta-actin mRNA concentration tended to be higher in patients with A3 and A4 Metavir activity grades compared with those with A0 and A1 activity grades. There was a significant correlation between the duration of HCV infection and both TGF-beta/beta-actin (r(2)=0.19, P=0.04) and IL-8/beta-actin mRNA concentrations (r(2)=0.19, P=0.03). IFN-gamma/beta-actin mRNA concentration also increased according to the duration of HCV (r(2)=0.19, P=0.07). Finally, there was a significant correlation between the duration of HCV infection and liver fibrosis stage (r(2)=0.17, P=0.045). Intrahepatic Th1 cytokine profile seems to be predominant in patients with extensive fibrosis and activity scores, suggesting that it might be responsible for liver injury in renal transplant patients.
Kamar
Nassim
N
Department of Nephrology, Dialysis and Multiorgan Transplantation, CHU Rangueil, Toulouse, France. kamar.n@chu-toulouse.fr
Rostaing
Lionel
L
Sandres-Saune
Karine
K
Selves
Janick
J
Barthe
Carole
C
Dubois
Martine
M
Alric
Laurent
L
Durand
Dominique
D
Izopet
Jacques
J
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000032:analysis* / Q000235:genetics; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics; D016030:Kidney Transplantation; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics
D016207:Cytokines; D016209:Interleukin-8; D012333:RNA, Messenger; D012367:RNA, Viral; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma