title: Diazepam treatment of pregnant rats differentially affects interleukin-1 and interleukin-2 secretion in their offspring during different phases of postnatal development.
abstract: Treatment of pregnant Long Evans rats with benzodiazepines was found to cause alterations in cellular immune responses in their offspring. We now report on changes in interleukin-1 (IL-1) and IL-2 secretion which were analyzed in rats from birth until 12 weeks. Time-pregnant rats were treated with diazepam (1.25 mg/kg/day subcutaneously) from gestational day 14 to 20. Lipopolysaccharide-stimulated release of macrophage-derived IL-1 by spleen cells, determined on D10.G4.1 cells, remained in the control range during the preweaning period (postnatal day 6-28), then decreased in prenatally diazepam-exposed offspring, significantly in males during the postweaning period (postnatal day 34-61) and in both sexes in adults (postnatal day 62-83). Concanavalin A-stimulated release of T lymphocyte-derived IL-2 from spleen cells, determined on CTLL-2 cells, was reduced in male and female offspring during preweaning (postnatal day 3-28) and postweaning (postnatal day 33-55) periods and normalized in adulthood (postnatal day 60-84). The percentage of IL-2 receptor expressing (CD25+) cells was unaffected. From these and our earlier data it is evident that prenatal exposure to low doses of benzodiazepines can result in long-lasting alterations of the cytokine network, as indicated by reduced release of TNF-alpha, IL-1, IL-6, IL-2 and interferon-gamma. The concomitant reduction of peripheral type benzodiazepine receptors on macrophages is discussed as a possible link between prenatal treatment and disturbed function.
authors.affiliation: Institute of Pharmacology, University of Zürich-Irchel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Schlumpf
authors.forename: W
authors.initials: W
authors.lastname: Lichtensteiger
authors.forename: H
authors.initials: H
authors.lastname: Ramseier
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D003975:Diazepam / Q000494:pharmacology*; D005260:Female; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism*; D007376:Interleukin-2 / Q000032:analysis / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000737:chemistry
chemical_list: D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D003975:Diazepam