Analysis of the effect of IL-12 therapy on immunoregulatory T-cell subsets in patients with chronic hepatitis C infection.
BACKGROUND/AIMS: Aim of this study was to investigate the influence of IL-12 therapy on the production of immunoregulatory type 1/type 2-cytokines by peripheral blood mononuclear cells from patients with chronic hepatitis C. METHODOLOGY: Peripheral blood mononuclear cells were isolated from 12 patients with chronic HCV infection before and after eight weeks of IL-12 application (0.03-0.5 micrograms/kg body weight). Peripheral blood mononuclear cells from 40 healthy blood donors served as a control group. The peripheral blood mononuclear cells were incubated for seven days with antigens stimulating specifically type 1 (tuberculin purified protein derivative) or type 2 T-cells (tetanus-toxoid). Furthermore, BCG (bacille Calmette-Guérin) was added to the cultures known to activate macrophages/antigen-presenting cells. Supernatants of peripheral blood mononuclear cells were analyzed for tuberculin purified protein derivative-induced production of the type 1 cytokine IFN-gamma, tetanus-toxoid-induced production of the type 2 cytokine IL-5 and the BCG-induced production of TNF-alpha by a double sandwich ELISA. RESULTS: IL-12 therapy hardly influenced the regulatory type 1/type 2 T-cell reactivity. In contrast, BCG induced secretion of TNF-alpha was significantly higher after eight weeks of IL-12 therapy (4348 +/- 3083 pg/mL) than before treatment (1559 +/- 988 pgmL, p < 0.01). Clinically, serum alanine transaminase levels significantly decreased during IL-12 treatment but HCV-RNA persisted in all patients. CONCLUSIONS: IL-12 therapy in patients with HCV does not alter the production of regulatory cytokines produced by type 1/type 2 TH cells. The significantly enhanced production of BCG-induced TNF-alpha may, however, indicate an activation of antigen presenting cells or natural killer cells.