Cytokine-mediated activation of macrophages from Mycobacterium bovis BCG- resistant and -susceptible mice: Differential effects of corticosterone on antimycobacterial activity and expression of the Bcg gene (candidate Nramp)

Abstract

Previous work in our laboratory has shown that corticosterone increases the susceptibility of macrophages from Bcg(s) mice to the growth of Mycobacterium avium. The innate antimycobacterial activity of macrophages from Bcg(r) mice was not affected by corticosterone. In contrast to the differential effect of corticosterone on the antimycobacterial activity of the macrophages, corticosterone suppressed the production of tumor necrosis factor alpha and nitric oxide by macrophages from both Bcg(r) and Bcg(s) mice. The purpose of this investigation was to compare the effects of corticosterone on the antimycobacterial activity of macrophages from Bcg(r) and Bcg(s) mice that have been activated in vitro with recombinant gamma interferon or granulocyte-macrophage colony-stimulating factor. We found that macrophages from both strains of congenic mice responded equally to the activation stimuli. The capacity of the activated macrophages from Bcg(s) mice to suppress the growth of M. avium was inhibited by the addition of corticosterone to the cultures. The addition of N(G)-monomethyl-L-arginine to the cultures did not affect the capacity of resident splenic macrophages from Bcg(r) mice to limit the growth of M. avium. However, N(G)-monomethyl-L- arginine reduced the capacity of gamma interferon-activated, but not granulocyte-macrophage colony-stimulating factor-activated, macrophages to limit the growth of M. avium by macrophages from both Beg(r) and Bcg(s) mice. The addition of corticosterone suppressed Nramp expression by macrophages from Bcg(s) mice. Nramp expression by macrophages from Bcg(r) mice was not affected by corticosterone.