Serum gamma-interferon-inducing factor (IL-18) and IL-10 levels in patients with acute hepatitis and fulminant hepatic failure

Background and Aims: The aim was to determine the role of T-helper (Th)1/Th2 cytokine responses in the clinical outcome of patients with acute liver injury. Methods: The serum levels of the cytokines, interleukin (IL)-18, gamma-interferon (IFN-γ), IL-10 and IL-4 were measured in 20 fulminant hepatic failure (FHF), 18 acute hepatitis (AH), 30 chronic viral hepatitis and 20 liver cirrhosis (LC) patients. Thirteen cases were from the intensive care unit (ICU) and there were 21 healthy volunteers. Immunohistochemical staining of liver biopsies for IL-18 expression was also performed. Results: Serum IL-18 levels in patients with FHF were significantly more elevated than in patients with other liver diseases, ICU cases and healthy volunteers. Furthermore, serum IFN-γ levels in patients with FHF were also significantly higher than in patients with chronic viral hepatitis, LC and healthy volunteers. We found a positive correlation between the levels of IL-18 and IFN-γ. However, no relationship was observed between these and clinical outcome. In immunohistochemical staining, CD68+ macrophage cells and IL-18-positive cells were observed in portal zones. Elevated serum IL-10 levels were restricted to patients presenting with FHF, and were significantly higher in surviving cases (P < 0.01). Furthermore, serum IL-10 levels, but not IL-4 levels, were inversely correlated with serum total bilirubin concentrations (P=0.045) and the death rate (p) outlined in Japan (P=0.030). Conclusion: These results suggest that IL-18 and IFN-γ are involved in the pathogenesis of acute hepatic injury in humans, and that, in particular, elevated serum levels of IL-10 may be predictive of improved outcomes for these patients.