Human monocytes produce IL-1 and an inhibitor of IL-1 in response to two different signals.
Recently, IL-1 inhibitors from urine, monocytes, or monocyte lines have been described. The relationship of these inhibitors to the production, release, and immunological effects of IL-1 is unclear. The present studies were initiated to describe and quantitate the production of IL-1 and a 23 to 45-kDa IL-1 inhibitor from human monocytes in response to certain stimuli using a mouse thymocyte system responsive to IL-1. Zymosan stimulated monocytes to produce IL-1 but not IL-1 inhibitor. Adherent immune complexes, human IgG1-4, and Fc fragments, but not F(ab')2, stimulated monocyte production of IL-1 inhibitor and little if any IL-1. Fibronectin and three of its fragments had neither effect. These observations suggest that monocytes produce IL-1 or IL-1 inhibitor in response to two different signals, through "endotoxin or beta-glucan" and Fc receptors, respectively. The inhibitor decreases IL-1-induced CD-1, C3H/HeJ, and D10 G4.1 cells but not IL-2-induced CD-1, C3H/HeJ, or CTLL-2 proliferation. The inhibitor competitively blocked binding of radiolabeled rIL-1 to the IL-1 receptor on murine thymoma cells. Preincubation of thymocytes with the inhibitor prevented IL-1-induced proliferation; however, this effect was reversed by washing thymocytes and inhibitor activity was markedly reduced when added 24 hr after stimulation with IL-1. These observations suggest that the inhibitor acts on IL-1 receptors to prevent thymocyte proliferation. Monocytes from patients with systemic lupus erythematosus produced less IL-1 inhibitor than cells from normal volunteers. The decrease in IL-1 inhibitor production may play a role in disease states.
Division of Rheumatology/Immunology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
P H
PH
Schur
D M
DM
Chang
P
P
Baptiste
L C
LC
Uhteg
D C
DC
Hanson
D000328:Adult; D000936:Antigen-Antibody Complex / Q000494:pharmacology; D003165:Complement System Proteins / Q000494:pharmacology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D007375:Interleukin-1; D003165:Complement System Proteins