Open AccessKilling of Mycobacterium tuberculosis within human monocytes: activation by cytokines and calcitriol
Author(s) -
DENIS M.
Publication year - 1991
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1991.tb08149.x
Subject(s) - lymphokine , mycobacterium tuberculosis , calcitriol , tubercle , recombinant dna , interferon gamma , immunology , microbiology and biotechnology , monocyte , biology , bacilli , cytokine , immune system , interleukin , vitamin d and neurology , tuberculosis , medicine , endocrinology , bacteria , biochemistry , pathology , genetics , gene
SUMMARY Human monocytes were isolated and their ability to harbour growth of virulent tubercle bacilli was assessed, in the presence or absence of various immunomodulators. Calcitriol (1,25 (OH 2 ), vitamin D 3 ) alone, at doses of 10 ‐7 ‐10 ‐9 m endowed human monocytes with a significant ability to restrict intracellular growth of the tubercle bacilli. Crude immune lymphokines as well as recombinant interferon‐gamma (IFN‐γ) endowed monocytes with no tuberoulostatic activity. Similarly, other recombinant cytokines tested, notably colony‐stimulating factor‐1 (CSF‐1), interleukin‐1 (IL‐1), interleukin‐3 (IL‐3) and interleukin‐6 (IL‐6) all failed to stimulate anti‐tuberculous properties, and even increased growth of the tubercle bacilli in monocytes, in the case of CSF‐1. Conversely, incubation of crude lymphokines in combination with calcitriol led to total stasis of the growth of M. tuberculosis . Experiments with recombinant cytokines and immunologically active vitamins showed that a combination of IFN‐γ tumour necrosis factor‐alpha and calcitriol induced a significant amount of intramonocyte killing of M. tuberculosis . Addition of this cocktail of factors to already infected monocytes fed to substantial killing of tubercle bacilli. These sets of experiments establish clearly that combinations of recombinant cytokines and vitamins may induce substantial intramonocyte killing of M. tuberculosis . The mechanism involved in this killing activity was not clarified.