Human T cells and interleukin 4 inhibit the release of interleukin 1 induced by lipopolysaccharide in serum-free cultures of autologous monocytes.
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.
Weiss
L
L
INSERM U 28, Hôpital Broussais, Paris, France.
Haeffner-Cavaillon
N
N
Laude
M
M
Cavaillon
J M
JM
Kazatchkine
M D
MD
D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D007376:Interleukin-2; D007377:Interleukin-3; D007378:Interleukins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor