IL-4 down-regulates IL-1 and TNF gene expression in human monocytes.
The effects of IL-4 on IL-1 and TNF gene expression in human peripheral monocytes (PBM) were examined. Highly purified PBM cultured for 24 to 96 h in the presence of IL-4 produce neither IL-1 nor TNF protein. RNA hybridization studies demonstrated that IL-4 does not induce transcription of IL-1 or TNF. Preincubation of PBM with IL-4 did, however, inhibit LPS-induced IL-1 and TNF production in a dose- and time-related fashion. Maximal inhibition occurred after 96 h of incubation with 200 U/ml IL-4. RNA hybridization studies demonstrated that IL-4 suppressed the expression of IL-1 alpha, IL-1 beta, and TNF mRNA. These results suggest IL-4 modulates monocyte production of TNF and IL-1 by down-regulation of gene expression. This unique property of IL-4 may be important in the regulation of the immune response.
Essner
R
R
Division of Surgical Oncology, UCLA School of Medicine, Los Angeles, CA 90024.
Rhoades
K
K
McBride
W H
WH
Morton
D L
DL
Economou
J S
JS
D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000502:physiology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*
D007166:Immunosuppressive Agents; D007375:Interleukin-1; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4