Background: An imbalance in Th1 and Th2 cytokine profiles may account for hepatic injury and failure to clear hepatitis C infection (HCV). In an animal model of viral hepatitis we have shown viral persistence is associated with Th2 cytokine profile and marked elevation of fgl2 / fibroleukin (fgl2), a macrophage mediator of inflammation. The aim of the study was to assess Th1 (IFN-g, IL-2), Th2 (IL-4, IL-10) cytokine profiles and fgl2 transcription in liver tissue from patients before and after therapy with interferon (INF) +/- ribivirin (Rib) and to correlate cytokine profiles to patients’ virologic response. Methods: Liver tissue was obtained from 29 HCV patients, all received either 6 or 12 months of therapy. Total cellular messenger RNA (mRNA) was isolated from hepatic tissue and complementary cDNA was generated by reverse transcriptase (RT) and then used for qualitative polymerase chain reaction (PCR). Pre-determined oligo-primers for cytokines IFN-g, IL-2, IL-4, IL-10 and fgl2 were used. Results: Adequate mRNA was obtained from 17/29 patients, in whom 10 had both pre and post treatment liver tissue and 7 with only pre treatment tissue. The genotypes (in treated patients) were 3a(4), 1a(4) and 1b(2). All had chronic hepatitis on liver biopsy.

In the SR (genotype 3a) patient IL-10 expression was lost with a decrease in fgl2 and an increase in IFN-g (Th1). In 1 patient with RR (genotype 1a) a decrease in fgl2 expression was observed. In 4/4 patients with PR (genotype 2×3a, 1a, 1b) there was decrease in IL-10 (Th2) and fgl2 with 1 patient showing increased expression of IFN- (Th1). Conclusions: IL-10 (Th2 activity) and fgl2 were present in all untreated HCV. Th1 (IFN-g) was not expressed in untreated HCV. Patients with a complete or partial response altered their cytokine profile to express IFN-g (Th1) and reduced fgl2 regardless of the therapeutic agent used.

Funded by Physician Services Incorporated Resident Research Grant

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