Lipoarabinomannan from Mycobacterium tuberculosis induces the production of tumour necrosis factor from human and murine macrophages

We show here that purified lipoarabinomannan (LAM) from Mycobacterium tuberculosis can cause the release of tumour necrosis factor (TNF) in vitro from human blood monocytes and activated mouse peritoneal macrophages, and the production of TNF in vivo in mice pretreated with Propionibacterium acnes, with a potency comparable to that of lipopolysaccharide (LPS) from Gram negative bacteria. Like LPS, LAM binds to polymyxin B. We confirmed that its activity was distinct from any contaminating LPS and was associated with the antigenic activity by affinity chromatography, using a monoclonal antibody specific for LAM. Treatment with dilute alkali greatly diminished the TNF-inducing activity, suggesting that omicron-acyl groups may be involved. When LAM was fractionated by electrophoresis on SDS-Page and blotted on nitrocellulose, most TNF-inducing capacity coincided with the bulk of the LAM, as estimated by molecular weight and antigenic activity. This modification of the Western blotting technique may be generally useful for the study of macrophage-triggering molecules. The ability of LAM to cause the release of TNF may be responsible for some of the characteristics of tuberculosis, such as fever, weight loss, raised acute phase reactants and necrosis that can be mediated by this cytokine.