Leukotriene D4 and indomethacin enhance additively the macrophage cytostatic activity in vitro towards MOPC-315 tumour cells.

Leukotriene C4, the precursor of leukotriene D4 (LTD4), was earlier shown to activate macrophages, as indicated by lysosomal enzyme discharge. This event is limited by LT-induced secretion of PGE2, which inhibits the functions of these cells. The circumstance that activated macrophages may exert cytostatic activity towards tumour cells prompted us to study the effect of LTD4 and indomethacin on the cytostatic activity of macrophages as expressed by inhibition of [3H]thymidine incorporation in MOPC-315 plasmacytoma tumour cells. Decrease in incorporation, caused by separate administration of the two substances, was additively enhanced upon exposure of the co-culture of macrophages and tumour cells to the two substances simultaneously. Tumour cells alone are not affected by the substances, but the low rate of thymidine incorporation by macrophages alone was increased by LTD4 in the presence of indomethacin. Decrease of thymidine incorporation into tumour cells co-cultured with macrophages is attributed to a macrophage-mediated, rather than to a direct, influence of LTD4 and indomethacin on tumour cells. An increase in macrophage-mediated cytostasis by LTD4 requires the inhibition of endogenous PGE2 production in macrophages.