Interleukin 18 induces a synergistic enhancement of interferon gamma production in mixed murine spleen cell-tumor cell cultures: Role of endogenous interleukin 12

Interleukin 18 (IL-18) reportedly synergizes with IL-12 and IL-10 for inter feron gamma (IFN-gamma) synthesis and natural killer (NK) cell activity, re spectively. Here we show that IL-18 alone induces low level IFN-gamma produ ction by unstimulated Balb/c mouse spleen cells, but production is enhanced synergistically in cocultures of spleen cells and allogeneic living or fix ed Yac-1 cells. Spleen cells could be primed with IL-18 prior to coculture with Yac-1 cells for IFN-gamma production, which also was observed in cocul tures containing either syngeneic or xenogeneic tumor cells. IFN-gamma prod uction in stimulated cocultures was abrogated almost completely by anti-IL- 12 antibody and was unrelated to spleen cell lytic activity. IL-10 moderate ly inhibited IFN-gamma production induced by IL-18. Therefore, in spleen ce ll and tumor cell cocultures exposed to IL-18, high levels of IFN-gamma are produced by the spleen cells arising from a synergistic interaction betwee n the exogenous IL-18 and endogenous IL-12; however, this activity is unrel ated to the spleen cell lytic activity.