Cytokine modulation of Mycobacterium tuberculosis growth in human macrophages

This study was concerned with the handling of ingested tubercle bacilli by normal human macrophages. Intracellular growth was determined after exposure of macrophages to viable bacilli in vitro and the effect of various cytokines, alone or in combination, on bacilli growth/survival was determined. It was found that Mycobacterium tuberculosis (M.tb) grew quite readily in untreated cultured human macrophages. Treatment with soluble factors showed that a crude lymphokine containing supernatant elicited with Concanavalin A (Con A) was ineffective at reducing growth of M.tb in vitro; similarly a crude lymphokine preparation from M.tb lysate-stimulated mononuclear cells failed to induce any mycobacteriostatic activity in human monocyte-derived macrophages. Recombinant cytokines were then evaluated for their ability to modulate growth of the tubercle bacilli in human macrophages. Recombinant interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and recombinant interleukin 4 (IL-4) were all ineffective at modifying M. tuberculosis growth in human macrophages. Recombinant tumour necrosis-alpha (TNF-alpha) curbed the growth of the bacilli in human macrophages in a reproducible fashion. No cytokine combination was more efficient than TNF-alpha alone. These studies thus highlight the resistance of virulent mycobacteria against different mechanisms of cytokine-induced macrophage bactericidal activity.