β2-adrenergic receptor stimulation inhibits nitric oxide generation by Mycobacterium avium infected macrophages

Catecholamine regulation of nitric oxide (NO) production by IFN gamma-primed macrophages infected with Mycobacterium avium was investigated. Epinephrine treatment of IFN gamma-primed macrophages at the time of M. avium infection inhibited the anti-mycobacterial activity of the cells. The anti-mycobacterial: activity of macrophages correlated with NO production. Using specific adrenergic receptor agonists, the abrogation of mycobacterial killing and decreased NO production by catecholamines was shown to be mediated via the beta 2-adrenergic receptor. Elevation of intracellular cAMP levels mimicked the catecholamine-mediated inhibition of NO in both M. avium infected and LPS stimulated macrophages. Specific inhibitors of both adenylate cyclase and protein kinase A prevented the beta 2-adrenoceptor-mediated inhibition of nitric oxide production. P2-adrenoreceptor stimulation at the time of M. avium infection of IFN gamma-primed macrophages also inhibited expression of iNOS mRNA. These observations show that catecholamine hormones can affect the outcome of macrophage-pathogen interactions and suggest that one result of sympathetic nervous system activation is the suppression of the capacity of macrophages to produce anti-microbial effector molecules. (C) 1999 Elsevier Science B.V, All rights reserved.