SELECTIVE INDUCTION OF TRANSFORMING GROWTH-FACTOR-BETA IN HUMAN MONOCYTES BY LIPOARABINOMANNAN OF MYCOBACTERIUM-TUBERCULOSIS

The induction of macrophage-deactivating (interleukin-10 [IL-10] and t ransforming growth factor beta [TGF-beta]) and macrophage-activating ( IL-1, IL-6, and tumor necrosis factor alpha [TNF-alpha]) cytokines by lipoarabinomannan (LAM) from pathogenic Mycobacterium tuberculosis Erd man and H37Rv strains (ManLAM) and nonpathogenic mycobacteria (AraLAM) in human blood monocytes was examined. ManLAM was significantly less potent in induction of TNF-alpha, IL-1, IL-6, and IL-10 protein and mR NA, whereas its ability to induce TGF-beta was similar to that of AraL AM. Differences in induction of TNF-alpha mRNA by the two LAM preparat ions only became apparent at late time points of culture (24 h). The i nduction of TNF-alpha and IL-1 by purified protein derivative of M. tu berculosis was significantly stronger than that by ManLAM. Pretreatmen t of monocytes with ManLAM did not, however, interfere with cytokine i nduction by lipopolysaccharide or AraLAM. The extensive mannosyl cappi ng of arabinose termini of ManLAM may underlie the lack of ability to induce some cytokines (IL-1, TNF-alpha, and IL-10) and the retained ab ility to induce TGF-beta. The latter may have a role in shifting the c ytokine milieu in favor of survival of M. tuberculosis.