Interferons antagonize gamma-ray-induced depression of natural immunity.

Abstract

The aim of this study was to determine the inhibitory effects of in vitro radiation on the number and function of natural killer (NK) cells and to investigate the capability of interferons (IFNs) to restore the activity of NK, depressed by gamma-rays. Mononuclear cells (MNC) were obtained from intact or in vitro irradiated (20 Gy) peripheral blood collected from healthy donors. Alternatively, MNC were irradiated (20 Gy) after separation from intact whole blood. The in vitro treatment of MNC with IFNs (alpha, beta, or gamma, 200 UI/ml) was performed at different times after or before radiation. The NK activity (4 h-51Cr release test), the percentage of CD16+/CD56+ cells and apoptosis (cytometric analysis), and binding (microscopic observation) were evaluated on Days 0, 1, 2, and 5 from gamma-ray exposure and IFNs treatment. The in vitro treatment of irradiated MNC with betaIFN after radiation completely reverses the inhibitory effects of gamma-rays on human NK activity. BetaIFN do not reduce the apoptosis induction by radiation and don't modify the number of CD16- or CD56-positive cells. The binding between irradiated effectors and tumor cells (K562) appears partially increased in betaIFN-treated MNC. The results of the present investigation suggest a possible role of betaIFN in reversing the detrimental effect of radiation on human natural immunity and provide a rational basis for in vivo use of betaIFN in cancer radiotherapy.