EFFECT OF LIPOARABINOMANNAN AND MYCOBACTERIA ON TUMOR-NECROSIS-FACTORPRODUCTION BY DIFFERENT POPULATIONS OF MURINE MACROPHAGES

Tumour necrosis factor (TNF) production is an important pathological m ediator in mycobacterial infections, and yet little is known of the fa ctors which influence its production. We have studied the influence of murine macrophage heterogeneity and activation state on TNF productio n following mycobacterial stimulation in vitro. Lipoarabinomannan (LAM ) from strains of Mycobacterium tuberculosis and Myco. avium different ially stimulated TNF production in thioglycollate-elicited macrophages in a dose-dependent manner. In comparison, resident peritoneal macrop hages produced much less TNF when stimulated with LAM, dead mycobacter ia or lipopolysaccharide (LPS). In contrast, zymosan stimulated reside nt macrophages to a higher degree than thioglycollate-elicited cells. Another comparison between bone marrow and thioglycollate-elicited mac rophages showed that both responded to LPS, but only the latter was st imulated significantly by H37Rv LAM. This may indicate that LAM stimul ation of macrophages takes place through a different pathway than both zymosan- and LPS-stimulated TNF production. Also, in vitro activation of peritoneal macrophages with interferon-gamma (IFN-gamma), increase d TNF response to several stimuli. Our studies indicate that the patho logy of mycobacterial infections through TNF production may be influen ced by the type and activation state of the macrophage which responds to that infection.