Interferon-gamma overcomes the glucocorticoid-mediated and the interleukin-4-mediated inhibition of interleukin-1 beta synthesis in human monocytes.
Interleukin-1 (IL-1) has been implicated in the tissue destruction of rheumatoid arthritis, a disease that is widely treated with glucocorticoids. In this study we investigated the effect of the T cell product interferon-gamma (IFN-gamma) on the glucocorticoid-mediated and on the IL-4-mediated inhibition of IL-1 beta mRNA and IL-1 beta protein synthesis in highly purified human monocytes. Both dexamethasone and IL-4 dose-dependently inhibited IL-1 beta mRNA and IL-1 beta protein synthesis after stimulation with LPS (300 ng/ml); maximal inhibition of 80-90% was achieved. IFN-gamma (1-100 U/ml) did not influence IL-1 beta mRNA and IL-1 beta protein levels in unstimulated cells, but potentiated the LPS-induced synthesis of IL-1 beta mRNA and IL-1 beta protein. After a preincubation time of 1 h, 100 U/ml of IFN-gamma increased the LPS-induced IL-1 beta production by about 20-40%. When human monocytes were preincubated for 1 h with IFN-gamma (100 U/ml) prior to the addition of dexamethasone (10(-6) M) and prior to the stimulation with LPS, the dexamethasone-mediated inhibition of IL-1 beta mRNA and IL-1 beta protein synthesis was totally neutralized by IFN-gamma. In addition, IFN-gamma totally overcame the negative effect of IL-4 (100 pM) on IL-1 beta protein synthesis. A preincubation period of at least 1 h with IFN-gamma was necessary for the neutralization of the dexamethasone effect. If IFN-gamma was given at the same time or after dexamethasone, only a weak effect was found.(ABSTRACT TRUNCATED AT 250 WORDS)
Geiger
T
T
Research Laboratories, Ciba-Geigy Ltd., Basel, Switzerland.
Arnold
J
J
Rordorf
C
C
Henn
R
R
Vosbeck
K
K
D015152:Blotting, Northern; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D011994:Recombinant Proteins
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma; D003513:Cycloheximide