Frequencies of interferon-γ and interleukin-10 secreting cells in peripheral blood mononuclear cells and liver infiltrating lymphocytes in chronic hepatitis B virus infection

Cytokine balance may play an important role in effective antiviral immunity. We determined the frequencies of interferon-gamma (IFN-gamma)-, interleukin-4 (IL-4)-, and interleukin-10 (IL-10)-secreting cells in response to HBV antigens in peripheral blood mononuclear cells (PBMCs) and liver-infiltrating lymphocytes (LILs) using an enzyme-linked immuno spot (ELISpot) assay and related them to serum ALT and HBV DNA levels, and hepatic histological findings. PBMCs were obtained from 25 patients with chronic hepatitis B, from eight of whom LILs were also obtained, and 12 healthy controls. On stimulation with hepatitis B core antigen (HBcAg), the median (range) frequencies of IFN-gamma- and IL-10-secreting cells were 25 (7-71) and 54 (26-101) cells/10(4) PBMCs, respectively, in patients with chronic hepatitis B, and 4 (0-12) and 36 (7-63) cells/104 PBMCs, respectively, in healthy controls. The frequencies of HBcAg-specific IFN-gamma-secreting cells in PBMCs and LILs of chronic hepatitis B patients correlated with serum ALT levels. Those of LILs correlated with serum ALT levels and HAI scores. In conclusion, HBcAg-specific IFN-gamma-secreting cells may play a role in liver damage in chronic HBV infection. Excessive IL-10 production by PBMCs and LILs in response to HBcAg may suppress antiviral immune responses and contribute to persistent infection. (C) 2003 Elsevier B.V. All rights reserved.