beta 2-adrenergic receptor stimulation inhibits nitric oxide generation byMycobacterium avium infected macrophages

Catecholamine regulation of nitric oxide (NO) production by IFN gamma-prime d macrophages infected with Mycobacterium avium was investigated. Epinephri ne treatment of IFN gamma-primed macrophages at the time of M. avium infect ion inhibited the anti-mycobacterial activity of the cells. The anti-mycoba cterial: activity of macrophages correlated with NO production. Using speci fic adrenergic receptor agonists, the abrogation of mycobacterial killing a nd decreased NO production by catecholamines was shown to be mediated via t he beta 2-adrenergic receptor. Elevation of intracellular cAMP levels mimic ked the catecholamine-mediated inhibition of NO in both M. avium infected a nd LPS stimulated macrophages. Specific inhibitors of both adenylate cyclas e and protein kinase A prevented the beta 2-adrenoceptor-mediated inhibitio n of nitric oxide production. P2-adrenoreceptor stimulation at the time of M. avium infection of IFN gamma-primed macrophages also inhibited expressio n of iNOS mRNA. These observations show that catecholamine hormones can aff ect the outcome of macrophage-pathogen interactions and suggest that one re sult of sympathetic nervous system activation is the suppression of the cap acity of macrophages to produce anti-microbial effector molecules. (C) 1999 Elsevier Science B.V, All rights reserved.