Human T cells and interleukin 4 inhibit the release of interleukin 1 induced by lipopolysaccharide in serumfree cultures of autologous monocytes

Abstract

Stimulation with lipopolysaccharide (LPS) of unfractionated peripheral blood mononuclear cells in serum-free cultures resulted in the release of lower amounts of interleukin (IL) 1 as compared with those induced in cultures of purified monocytes. In addition, a dose-dependent decrease in IL 1 production was observed when purified autologous T cells were added to cultures of LPS-stimulated monocytes. The inhibitory effect of T cells on IL 1 production was reproduced by adding human recombinant IL 4 to monocyte cultures. IL 4 optimally inhibited the generation of cell-associated IL 1 and the extracellular release of IL 1 in monocyte cultures performed in the presence of low doses of LPS. IL 4 inhibited the generation of IL 1 activity and that of IL 1 alpha and IL 1 beta antigens indicating that IL 4 interfered with IL 1 transcription and/or processing rather than induced the synthesis of an IL 1 inhibitor. IL 2 and IL 3 enhanced IL 1 production by LPS-stimulated cells whereas granulocyte-monocyte colony-stimulating factor had no effect. IL 4 inhibited the production and the release of tumor necrosis factor alpha activity by monocytes stimulated with LPS. Thus, T cells and IL 4 may down-regulate the production of monokines which induce their proliferation and exert a suppressive effect on the generation of potent proinflammatory mediators.