SYMPATHETIC NEURAL RESPONSE TO IMMUNE SIGNALS INVOLVES NITRIC-OXIDE -EFFECTS OF EXPOSURE TO ALCOHOL IN-UTERO

In response to infection, inflammation, or injury, the neural-immune-e ndocrine networks are activated to restore or maintain stability in th e internal environment. Disruption of any one of the functional compon ents map impair the effectiveness of the immune response to challenges , and may consequently jeopardize the wellness of the host. Studies in the author's laboratory have shown that the normal activation of sple nic sympathetic neurons in response to the endotoxin lipopolysaccharid e, a tool frequently used to mimic infection or inflammation, does not occur in fetal alcohol-exposed (FAE) rats. The sympathetic innervatio n of lymphoid organs is considered an important immune modulator. Thus , the anomalous splenic sympathetic response may partly account for th e impaired immunity associated with FAE. Although the underlying mecha nism is far from clear, studies described in this report suggest that nitric oxide (NO), a gaseous free radical, is involved in the altered splenic sympathetic neural response to immune signals. The suggestion is supported by the following findings: (1) blockade of NO synthesis p revented the blunted sympathetic response to lipopolysaccharide or int erleukin-l in FAE rats, and (2) there was a further increase in NO for mation in response to lipopolysaccharide in the FAE rats compared to t heir control cohorts. This was demonstrated by an augmented increase i n the inducible NO synthase immunoreactivity in the spleen as well as in circulating levels of NO metabolites. It is suggested, therefore, t hat the altered splenic sympathetic response to immune signals involve s excessive formation of NO that may account, at least in part, for th e impaired immunity associated with FAE. (C) 1998 Elsevier Science Inc .