CHARACTERISTICS OF BACTERIAL LIPOPOLYSACCHARIDE INDUCTION OF INTERLEUKIN-1 SYNTHESIS AND SECRETION BY HUMAN-MONOCYTES

Abstract

The objective of these studies was to characterize some aspects of interleukin 1 (IL-1) synthesis and secretion by human monocytes after stimulation with bacterial lipopolysaccharides (LPS). Various molecular species of LPS were incubated with adherent monocytes for 24 h. IL-1 actvity in monocyte supernatants (secretion) and lysates (synthesis) was determined by stimulation of collagenase production in rabbit articular chondrocytes and augmentation of mitogen-induced proliferation of murine thymocytes. The presence of cytochalasin B enhanced LPS-induced IL-1 secretion wtihout altering IL-1 synthesis. Monocytes preincubated in dexamethasone or hydrocortisone failed to exhibit any IL-1 activity in supernatants after LPS stimulation but the cell lysates still possessed 50% of control IL-1 activity. Studies with different LPS preparations indicated that the presence of diphosphoryl groups in lipid A enhanced the IL-1-inducing activities. Butanol-extracted LPS preparations, containing associated proteins, were not completely inhibited by 5 .mu.g/ml polymyxin B in induction of IL-1 production at LPS concentrations of 10 or 100 ng/ml. These results indicate that the failure of polymyxin B to inhibit stimulation of IL-1 production by tests materials cannot be assumed to mean an absence of contaminating LPS.