EFFECTS OF IMMUNE-COMPLEXES ON PRODUCTION BY HUMAN-MONOCYTES OF INTERLEUKIN-1 OR AN INTERLEUKIN-1 INHIBITOR

The ability of phorbol myristic acetate (PMA), Fc fragments, and various forms of immune complexes to induce the production by human monocytes of factors stimulatory to chondrocytes or thymocytes was examined. All of these materials were prepared free of detectable contamination with bacterial lipopolysaccharides (LPS) at the level of < 0.1 ng/ml. Supernatants and lysates from stimulated human monocytes were assayed for their ability to induce collagenase production in cultured rabbit articular chondrocytes or to augment mitogen-induced proliferation of murine thymocytes. The activity detected by these assays exhibited a MW .apprx. 15,000 and electrophoretic heterogeneity in the pH ranges 5-5.5 and 6.5-7.0, characteristics of human interleukein 1 (IL 1) or IL 1-like factors. Monocytes cultured with 2 ng/ml LPS produced chondrocyte and thymocyte stimulatory fctors. PMA; Fc fragments; and soluble, precipitated, particulate or adherent immune complexes were inactive in stimulating the monocytes. However, complement fixation by precipitated immune complexes did generate activity capable of inducing monocytes to synthesize and secrete chondrocyte and thymocyte stimulatory factors. Adherent immune complexes and PMA were biologically active, as evidenced by induction of superoxide generation in the human monocytes. Supernatants from monocytes cultured on adherent immune complexes contained a factor inhibitory to chondrocyte and thymocyte responsiveness. This factor had a MW .apprx. 22,000 and appeared to inhibit specifically IL 1 stimulation, not IL 2 stimulation or cell proliferation. It was concluded that PMA, Fc fragments and various forms of immune complexes in the absence of complement do not induce IL 1 production in human monocytes. However, complement fixation by immune complees does lead to activation of monocytes to produce IL 1. Monocytes cultured on adherent immune complexes produce an IL 1 inhibitor.