Suppression by Interleukin 4 of Activation of Human Blood Monocytes to the Tumoricidal State

The effect of interleukin 4 (IL‐4) on expression of antitumor activity of blood monocytes purified by counter‐flow centrifugal elutriation from healthy donors was examined. The blood monocytes were incubated for 24 h in medium with lipopolysaccharide, interferon γ (IFN‐γ) or desmethyl muramyl dipeptide (norMDP) or with IFN‐γ and norMDP in the presence of IL‐4, and then their tumoricidal activity was assayed by measuring (125)IUdR release from human melanoma (A375) cells. Irrespective of activation stimulus, addition of IL‐4 to cultures of monocytes and activators resulted in dose‐dependent suppression of the tumoricidal activity of monocytes against parent A375 melanoma cells and the variant cells, A375‐R resistant to IL‐1 and tumor necrosis factor α. IL‐4 suppressed the early induction phase of monocyte activation. Rabbit anti‐IL‐4 antisera completely blocked the IL‐4‐mediated suppression of monocyte activation to the tumoricidal state. These findings suggest that IL‐4 is important in vivo in down‐regulation of anti‐tumor expression of monocytes.