Type 1 interferon as an antiinflammatory agent: inhibition of lipopolysaccharide-induced interleukin-1 beta and induction of interleukin-1 receptor 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 diluted 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. There was no detectable induction of TNF-alpha, 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-1 beta when added to the diluted blood samples before LPS addition. However, neither IFN had any effect on IL-1 beta 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-1 beta production, but at 1000 pg/ml or greater there was significant inhibition of IL-1 beta production. These results suggest that type I IFNs play a role in regulating the inflammatory response.
Huang
Y
Y
Department of Biology, Indiana University, Bloomington 47405, USA.
Blatt
L M
LM
Taylor
M W
MW
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000096:biosynthesis; D012795:Sialoglycoproteins / Q000096:biosynthesis*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; C507763:IL1RN protein, human; D007369:Interferon Inducers; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D007371:Interferon-gamma; D006493:Heparin