ROLE OF CYTOKINES IN TUBERCULOSIS

Mycobacterium tuberculosis and Mycobacterium bovis are facultative int racellular pathogens which preferentially utilize the macrophage as th eir host cell. Acquired resistance against mycobacteria depends on T c ells which activate antimicrobial macrophage functions via the release of cytokines. The data summarized below suggest an important role for interferon-gamma (IFN-gamma) as well as the B cell-stimulatory factor s interleukin-4 (IL-4) and IL-6 in the induction of tuberculostatic ma crophage functions. Growth inhibition of mycobacteria by cytokine-stim ulated macrophages is mediated by reactive nitrogen intermediates (RNI ) derived from L-arginine. Tumor necrosis factor-alpha (TNF-alpha) and IL-10 act as autocrine regulators in the induction of the enzyme NO-s ynthase. Both cytokines are produced by macrophages stimulated with IF N-gamma and infected with M. bovis. While TNF-alpha mediates activatio n of the NO-synthase and production of RNI, IL-10 suppresses this enzy me activity. The outcome of mycobacterial infection is probably regula ted by a complex network between stimulatory and inhibitory cytokines.