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 gamma (IFN-gamma) or desmethyl muramyl dipeptide (norMDP) or with IFN-gamma and norMDP in the presence of IL-4, and then their tumoricidal activity was assayed by measuring 125IUdR 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 alpha. 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.
Nishioka
Y
Y
Third Department of Internal Medicine, University of Tokushima School of Medicine.
Sone
S
S
Okubo
A
A
Ogura
T
T
D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008545:Melanoma / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4