Type 1 Interferon as an Antiinflammatory Agent: Inhibition of Lipopolysaccharide-Induced Interleukin-lβ and Induction of Interleukin-1 Receptor Antagonist

Abstract

The effect of two type 1 interferons (r-metIFN-conl and IFN-α_2b) on tne induction of specific cytokines and IL-1Ra in whole blood was examined. IFN-γ was induced at low levels following treatment of diluted whole blood in some but not all subjects. IL-1Ra was induced by both r-metIFN-conl and IFN-α_2b, but with 10-to 100-fold higher induction per ng IFN with r-metIFN-conl than with IFN-γ_2b. There was no detectable induction of TNF-α, IL-4, or IL-6 by either IFN. The effect of both IFN preparations was measured on LPS-induced inflammatory cytokines. Both IFN preparations inhibited the production of IL-1β when added to the diluted blood samples before LPS addition. However, neither IFN had any effect on IL-1β synthesis when added at the same time or after LPS induction. When added to total blood cells in the absence of LPS at low concentration (up to 100 pg/ml), IFN slightly stimulated IL-1β production, but at 1000 pg/ml or greater there was significant inhibition of IL-1β production. These results suggest that type I IFNs play a role in regulating the inflammatory response.