Elevated intracellular IFN-γ levels in circulating CD8+ lymphocytes in patients with fulminant hepatitis

Background/Aims: Fulminant hepatitis usually takes a rapidly progressive course, terminating in death within a short period. Experimental studies have demonstrated that immunological mechanisms play an important role, especially those involving virus-specific CD8+ cytotoxic T lymphocytes and their production of interferon-gamma (IFN-γ). However, there are no immunological markers for prediction of the development of fulminant hepatitis in man. Methods: Peripheral blood lymphocytes from four patients with fulminant hepatitis, six with acute hepatitis and 11 healthy volunteers as normal controls were analyzed. Intracellular IFN-γ production in both CD8 positive and negative T lymphocytes was assessed by flow cytometry. Results: Populations of CD8+ IFN-γ+ T lymphocytes were significantly increased in patients with fulminant hepatitis, as compared with those with acute hepatitis and normal controls. Production of IFN-γ in CD8+ T lymphocytes of patients with fulminant hepatitis was also elevated, furthermore significantly correlating with the prothrombin time (r=−0.64, p<0.01). Conclusions: The capacity for IFN-γ production by CD8+ lymphocytes is up-regulated in fulminant hepatitis, and this may be important for the development of fulminant hepatitis.