Macrophage cytokines render WEHI-3B tumor cells susceptible to cytostasis by prostaglandins.

The growth of the murine myelomonocytic leukemia tumor, WEHI-3B, has been shown to be inhibited by a two-step treatment: first, incubation for one hour with either interleukin-1 (human recombinant IL-1 alpha or tumor necrosis factor (human recombinant TNF-alpha); second, subsequent exposure to prostaglandins. Preincubation with IL-1 rendered the tumor cells more susceptible to subsequent treatment with either prostaglandin E2 or to the stable synthetic analogue of prostacyclin DC-PGI2. Preincubation with TNF-alpha rendered the tumor cells more susceptible to further treatment with PGE2 but not with DC-PGI2. Preconditioning of the tumour cells with either IL-1 alpha or TNF alpha did not affect cytostasis by subsequent culture of tumor cells in presence of either one of the cytokines. It is concluded that the interactions between macrophage cytokines and prostaglandins in enhancement of antitumor activity might imply first binding or induction of certain modifications in the tumor cells by the cytokines which render the cells more susceptible to exposure to prostaglandins.