Mouse recombinant interferon-beta augments the induction of macrophage cytolytic activity by interleukin-2 in vitro

We investigated the augmenting effect of mouse recombinant interferon-beta (MurIFN-beta) on the induction of macrophage (M phi) cytolytic activity by interleukin-2 (IL-2). C3H/He spleen cells were cultured with various doses of recombinant (r) IL-2 and/or MurIFN-beta for 4 days, and their cytotoxic activities against syngeneic M phi were assessed by a 4-h 51Cr-release assay. Although MurIFN-beta itself induced little M phi cytolytic activity, it significantly augmented the IL-2-induced cytotoxicity against M phi. MurIFN-beta showed a dose-dependent enhancement on the induction of anti-M phi activity by IL-2 with a peak at 2,000-10,000 U/ml, and the augmenting effect of rIFN-beta was more marked on lower doses of rIL-2 than on higher doses. This augmenting effect was also observed in IFN-alpha, whereas IFN-gamma showed no influence on IL-2-induced anti-M phi activity. The phenotype analysis by depletion technique with antibody and completement showed that anti-M phi effectors induced by either rIL-2 or the combination of rIL-2 and rIFN-beta were Thy-1+, asialoGM1+, L3T4-, and Ly2-. These results suggest that IFN-alpha or IFN-beta has a synergistic effect with IL-2 on the induction of nonspecific killer cells with M phi cytolytic activity.