INDUCTION OF INFLAMMATORY CYTOKINES BY A SOLUBLE MOIETY PREPARED FROM AN ENZYME LYSATE OF ACTINOMYCES-VISCOSUS CELL-WALLS

A carbohydrate-rich and immunobiologically active component, M1Av, was prepared from an M-1 endo-N-acetylmuramidase digest of cell walls of Actinomyces viscosus ATCC 19246 by CM Sephadex C-25 and Sephadex G-100 chromatography. M1Av stimulated thioglycolate-induced peritoneal macrophages from C3H/HeN and C3H/HeJ mice to release cell-free tumour necrosis factor (TNF) and interleukin (IL)-6, and a cell-associated thymocyte activating factor, probably IL-1. An intravenous (i.v.) injection of M1Av induced increased levels of TNF and IL-6 in the serum of C3H/HeN mice that had been primed with 100 mug of muramyldipeptide (MDP) i.v. However, M1Av did not induce TNF release in C3H/HeJ mice similarly primed with MDP. Simultaneous administration of M1Av (100 mug, i.v.) and galactosamine (18 mg, intraperitoneally) killed C3H/HeN, but not C3H/HeJ mice. M1Av was shown to be practically free of endotoxin by the Limulus test. These findings indicate that the solubilised A. viscosus cell-wall carbohydrate moiety induced inflammatory cytokines both in vitro and in vivo.