Normal human neutrophils are a source of a specific interleukin 1 inhibitor.
In the course of our study on neutrophil production of an interleukin 1 (IL-1)-like factor, we found that the addition of polymorphonuclear neutrophils (PMN) to monocytes cultured in the presence of zymosan resulted in decreased IL 1 activity of the resultant supernatant, suggesting that PMN may contain an inhibitor of IL 1. The objective of this investigation was to study this IL 1 inhibitor which normal human PMN contain. The inhibitor is constitutively present in the PMN because 0 hr PMN lysates and unstimulated PMN supernatants also show inhibitory activity. The PMN inhibitor inhibits IL 1 (crude and partially purified) in a dose-response manner and does not affect basal [3H]thymidine incorporation in the presence or absence of PHA-P. The PMN inhibitor does not have any effect on interleukin 2 (IL 2)-induced proliferation of the IL 2-dependent CTLL cells. The inhibitor can be generated in the absence of serum and is not produced as a result of proteolytic activity from PMN enzymes. The inhibitor is heat-labile and is most stable at neutral pH. Gel filtration studies on Sephadex G-200 indicate that the inhibitor is heterogeneous in size. Two inhibitory peaks, at 45,000 to 70,000 m.w. and at greater than 160,000 m.w., were observed. When zymosan-stimulated PMN supernatant was chromatographed, there was separation of inhibitory factor from a 17,000 m.w. proliferating factor. Presence of this PMN inhibitor may be important in negative regulation of IL 1.
D002460:Cell Line; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D008213:Lymphocyte Activation / Q000187:drug effects; D008970:Molecular Weight; D009504:Neutrophils / Q000032:analysis / Q000276:immunology*; D011480:Protease Inhibitors / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D015054:Zymosan / Q000494:pharmacology
D007375:Interleukin-1; D007376:Interleukin-2; D011480:Protease Inhibitors; D015054:Zymosan