Regulation of mycobacterial growth by the hypothalamus-pituitary-adrenal axis: Differential responses of Mycobacterium bovis BCG-resistant and - susceptible mice

The role of the hypothalamus-pituitary-adrenal (HPA) axis in regulating the growth of Mycobacterium avium in Mycobacterium bovis BCG-resistant and - susceptible congenic mice was evaluated. Restraint was used to activate the HPA axis, which resulted in an increase in the level of corticosterone in the plasma. Activation of the HPA axis increased the susceptibility of BALB/c.Bcg(s) mice to the growth of M. avium. In contrast, the growth of M. avium was not altered in BALB/c.Bcg(r) mice as a result of HPA activation. Adrenalectomy abolished the effect of HPA activation on mycobacterial growth, as did treatment of the mice with a glucocorticoid receptor antagonist, RU 486. Activation of the HPA axis also resulted in the increased susceptibility of splenic macrophages from Bcg(s) mice but not from Bcg(r) mice to M. avium growth in vitro. The production of tumor necrosis factor alpha and of reactive nitrogen intermediates by splenic macrophages from both strains of mice was suppressed as a result of HPA activation. The implications of these findings for resistance controlled by Bcg and for susceptibility to mycobacterial growth are discussed.