Influences of interleukins 2 and 4 on tumor necrosis factor production by murine mononuclear phagocytes.
Administration of recombinant human interleukin 2 (IL-2) to mice gave rise to peritoneal macrophages and blood monocytes that were primed to produce large amounts of tumor necrosis factor (TNF). Macrophages from IL-2-treated athymic mice responded less well than those from euthymic mice. In addition to its in vivo priming effect, IL-2 was able to directly stimulate TNF production in vitro by purified monocytes. Macrophages responded to IL-2 generally less well than monocytes both in vitro and in vivo. In contrast to IL-2, recombinant murine interleukin 4 (IL-4) down-regulated TNF synthesis by macrophages. In vitro pretreatment of macrophages with IL-4 largely abolished their ability to synthesize TNF in response to IL-2 or lipopolysaccharide. Also, administration of IL-4 to mice blocked the ability of IL-2 and lipopolysaccharide to prime macrophages in vivo for TNF production. Overall, these results demonstrate that IL-2 and IL-4 can act antagonistically to regulate TNF production by macrophages. In spite of its down-regulatory action on TNF production, IL-4 was unable to protect mice against the lethal toxic effects of lipopolysaccharide or IL-2.
McBride
W H
WH
Department of Radiation Oncology, Jonsson Comprehensive Cancer Center, Los Angeles, California.
Economou
J S
JS
Nayersina
R
R
Comora
S
S
Essner
R
R
D000818:Animals; D007376:Interleukin-2 / Q000494:pharmacology* / Q000633:toxicity; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007376:Interleukin-2; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4