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Modulation of Mycobacterium avium Growth in Murine Macrophages: Reversal of Unresponsiveness to Interferon‐Gamma by Indomethacin or Interleukin‐4
Author(s) -
Denis Michel,
Gregg Evan O.
Publication year - 1991
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.49.1.65
Subject(s) - biology , interferon gamma , microbiology and biotechnology , virulence , macrophage , cytokine , interleukin 4 , interleukin , peritoneal cavity , mycobacterium , interferon , tumor necrosis factor alpha , immunology , in vitro , bacteria , biochemistry , genetics , anatomy , gene
The ability of soluble factors to modulate the growth of a virulent strain of Mycobacterium avium in murine peritoneal macrophages was studied. The virulent strain, TMC 702, grew progressively in the organs of susceptible BALB/C mice. In addition, this strain of M. avium grew progressively in untreated peritoneal macrophages. Treatment of macrophage monolayers with interferon‐gamma (IFN‐γ) did not change significantly the intracellular growth of M. avium. Addition of indomethacin to IFN‐γ‐treated macrophage monolayers rendered them significantly more bacteriostatic than macrophages treated with interferon alone, suggesting a role for prostaglandins in inducing unresponsiveness to IFN‐γ in infected cells. Additionally, treatment with tumour necrosis factor‐alpha led to a modest increase in bacteriostasis, as compared to untreated monolayers. Further experiments with recombinant interleukins showed that interleukin‐4 (IL‐4), on its own, could increase bacteriostatic activity against M.avium in a reproducible fashion. Experiments with interleukin combinations showed that IFN‐γ and IL‐4 treatment of macrophages rendered these cells almost fully bacteriostatic against M . avium. Inclusion of scavengers of reactive oxygen species did not modify the beneficial effect of IFN‐γ and IL‐4. Overall, our results suggest an important role for interleukins in modulating the interaction between virulent mycobacteria and murine macrophages.