TYPE-1 INTERFERON AS AN ANTIINFLAMMATORY AGENT - INHIBITION OF LIPOPOLYSACCHARIDE-INDUCED INTERLEUKIN-1-BETA AND INDUCTION OF INTERLEUKIN-1RECEPTOR ANTAGONIST

The effect of two type 1 interferons (r-metIFN-con1 and IFN-alpha(2b)) on the induction of specific cytokines and IL-1Ra in whole blood was examined. IFN-gamma was induced at low levels following treatment of d iluted whole blood in some but not all subjects. IL-1Ra was induced by both r-metIFN-con1 and IFN-alpha(2b), but with 10- to 100-fold higher induction per ng IFN with r-metIFN-con1 than with IFN-alpha(2b). Ther e was no detectable induction of TNF-alpha, IL-4, or IL-6 by either IF N. The effect of both IFN preparations was measured on LPS-induced inf lammatory cytokines. Both IFN preparations inhibited the production of IL-1 beta when added to the diluted blood samples before LPS addition . However, neither IFN had any effect on IL-1 beta synthesis when adde d at the same time or after LPS induction. When added to total blood c ells in the absence of LPS at low concentration (up to 100 pg/ml), IFN slightly stimulated IL-1 beta production, but at 1000 pg/ml or greate r there was significant inhibition of IL-1 beta production. These resu lts suggest that type I IFNs play a role in regulating the inflammator y response.