Interferons as inhibitors of interleukin 1 induced interleukin 1 synthesis.
IL-1 induces its own gene expression in cultured smooth muscle and endothelial cells and in human PBMC. IL-1-induced IL-1 may be part of a self-amplification or autocrine event in inflammation. In the present study IFN gamma consistently increased LPS-induced IL-1, but reduced the total amount of IL-1-induced IL-1 from PBMC. On a molar basis, IFN gamma and IFN alpha 2 were equally effective. IL-6 also reduced IL-1 induced IL-1 but was approximately 300-fold less potent than the two interferons. The augmentation of LPS-stimulated IL-1 by IFN gamma was observed only when added at the same time as LPS, but IFN gamma could be added several hours after stimulation with IL-1 and still suppress IL-1 production. LPS-induced mRNA for IL-1 beta at 4 hours was enhanced by IFN gamma whereas IL-1-induced IL-1 beta mRNA was reduced by 70% in the presence of IFN gamma and this reduction was not due to increase degradation of IL-1 beta mRNA. These results suggest that in inflammatory tissues where IL-1 self amplification of its own gene expression is part of the pathological process, interferons may act to inhibit this cycle.
Schindler
R
R
Department of Medicine, Tufts University School of Medicine, Boston, MA.
Ghezzi
P
P
Dinarello
C A
CA
D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D007370:Interferon Type I; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007371:Interferon-gamma; D007372:Interferons