Effects of stress on alveolar macrophages: A role for the sympathetic nervous system

Alveolar macrophages (AMs) play an important role in the regulation of the local immune reactivity in the lung. It was previously shown that exposure of rats to mild inescapable electrical footshock stress (20 min, 4 shocks/m in, 5 s/shock, 0.8 mAmp) leads to apparent changes in the activity of AMs u pon stimulation, reflected by an enhanced interleukin-1 beta and tumor necr osis factor-alpha secretion and decreased nitric oxide secretion compared w ith the secretion by AMs isolated from nonstressed rats. Here we show that in vivo blockade of the autonomic nervous system by intraperitoneal injecti on of the nicotinic receptor antagonist chlorisondamine leads to complete a brogation of these stress-induced alterations in AM activity. This role fur the autonomic nervous system could further be attributed to sympathetic st imulation of beta-adrenergic receptors as shown by blockade of beta-adrenoc eptors. Blockade of either alpha-adrenoceptors or parasympathetic output di d not result in abrogation of the stress-induced changes in AM activity. Th e beta-adrenergic modulation of AM activity most likely is not due to a dir ect effect of catecholamines on AMs because mimicking the in vivo stress ef fects by in vitro preincubation of AMs with various doses of catecholamines followed by lipopolysaccharide stimulation did not result in an altered cy tokine secretion by AMs.