title: Gestational nicotine exposure alone or in combination with ethanol down-modulates offspring immune function.
abstract: Prenatal nicotine exposure has been shown to disrupt the development of a number of peripheral organs. In the current study, we examined the effects of gestational nicotine exposure, alone or in combination with ethanol exposure, on offspring immune function. Timed pregnant rats were treated with either nicotine (6 mg/kg/day) from gestation day 4-20 using subcutaneously implanted osmotic mini-pumps or ethanol administered in the drinking water (15% w/v) from gestation day 10-20. The combined exposure group received both treatments. The ability of offspring T and B cells to proliferate in response to nonspecific stimulation by Concanavalin A or lipopolysaccharide, respectively, was determined on postnatal days 9, 15, 22, 29, 64, and 86. Offspring splenocyte beta(2)-adrenoceptor binding was also measured. Nicotine or nicotine+ethanol suppressed splenocyte responsiveness to Concanavalin A or lipopolysaccharide which was similar in timing and magnitude to that seen with ethanol alone. Splenocytes from these groups remained subresponsive to stimulation well into adulthood. The combined drug treatment caused an overall reduction in spleen beta-adrenergic receptor binding whereas the individual drug treatments did not alter the development of spleen beta-adrenergic receptors.Our results indicate that prenatal nicotine exposure can cause long-term suppression of the proliferative response of offspring immune cells. Moreover, the effects of nicotine+ethanol may cause more severe deficits in adulthood.
authors.affiliation: Centers of Bioorganic Chemistry and Life Sciences and Toxicology, Research Triangle Institute, PO Box 12194, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA. pvb@rti.org
authors.forename: P V
authors.initials: PV
authors.lastname: Basta
authors.forename: K B
authors.initials: KB
authors.lastname: Basham
authors.forename: W P
authors.initials: WP
authors.lastname: Ross
authors.forename: M E
authors.initials: ME
authors.lastname: Brust
authors.forename: H A
authors.initials: HA
authors.lastname: Navarro
mesh_terms: D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007108:Immune Tolerance / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects
chemical_list: D011943:Receptors, Adrenergic, beta; D003208:Concanavalin A; D000431:Ethanol; D009538:Nicotine