THE ROLE OF GAMMA-INTERFERON, VITAMIN-D3 METABOLITES AND TUMOR-NECROSIS-FACTOR IN THE PATHOGENESIS OF TUBERCULOSIS

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  • 1 October 1987
    • journal article
    • research article
    • Vol. 62  (2) , 229-234
Abstract
Endotoxin (LPS)-triggered release of tumour necrosis factor (TNF) from human monocyes is high for the first 3 days in culture, and then falls to a trough between Days 4 and 6. This trough is less deep if the cells are cultured in the presence of indomethacin. If monocytes are cultured in the presence of either recombinant gamma-interferon or 1,25-(OH)2 vitamin D3, their capacity for LPS-triggered TNF release is increased. Live virulent Mycobacterium tuberculosis can substitute for the lPS, and is markedly more effective as a trigger than several strains of BCG prepared in an identical manner. Since secretion of IFN-.gamma. and conversion of circulating 25-(OH) vitamin D3 to the active dihydroxy metabolite by interferon-activated macrophages probably occur in tuberculosis, we suggest that triggering of TNF release from the resulting activated macrophage populations might explain much of the weight loss and tissue damage that characterize this disease. IFN-.gamma. does not activate effective anti-myobacterial mechanisms in human monocytes, so its role in tuberculosis may be immunopathological rather than protective.