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-endocrine networks are activated to restore or maintain stability in the internal environment. Disruption of any one of the functional components may 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 splenic sympathetic neurons in response to the endotoxin lipopolysaccharide, a tool frequently used to mimic infection or inflammation, does not occur in fetal alcohol-exposed (FAE) rats. The sympathetic innervation of lymphoid organs is considered an important immune modulator. Thus, the anomalous splenic sympathetic response may partly account for the impaired immunity associated with FAE. Although the underlying mechanism 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 prevented the blunted sympathetic response to lipopolysaccharide or interleukin-1 in FAE rats, and (2) there was a further increase in NO formation in response to lipopolysaccharide in the FAE rats compared to their control cohorts. This was demonstrated by an augmented increase in the inducible NO synthase immunoreactivity in the spleen as well as in circulating levels of NO metabolites. It is suggested, therefore, that the altered splenic sympathetic response to immune signals involves excessive formation of NO that may account, at least in part, for the impaired immunity associated with FAE.
Department of Neurobiology and Anatomy, University of Texas Medical School, Houston 77225, USA.
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D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007109:Immunity; D008070:Lipopolysaccharides / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013154:Spleen / Q000276:immunology / Q000294:innervation; D013564:Sympathetic Nervous System / Q000502:physiology*
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D000431:Ethanol