Impaired host resistance to Trichinella spiralis as a consequence of prenatal treatment of rats with diazepam.
In utero exposure of Long Evans rats to low dosages of diazepam has previously been found to result in depression of cellular and humoral immune responses until adulthood, with marked changes in cytokine release by splenocytes and splenic macrophages. In order to assess the significance of these alterations in immune cells with regard to host resistance, we investigated the resistance of adult offspring towards Trichinella spiralis. Time-pregnant rats were treated with diazepam (1.25 mg/kg/day) or vehicle from gestational day 14 to 20. Male offspring were infected with T. spiralis at 2 months of age. This infection model tests the participation of T- and B-cell populations and of macrophages. Prenatally diazepam-exposed animals exhibited an impaired defence towards T. spiralis. The number of muscle larvae was increased as determined in digested carcasses and by morphometric analysis of the tongue. Moreover, antibody titers were altered, i.e., IgG was decreased and IgA was elevated in the prenatally diazepam-exposed group. These results demonstrate an impaired defense towards T. spiralis in adult rats after prenatal exposure to diazepam.
Schlumpf
M
M
Institute of Pharmacology, University of Zürich, Switzerland.
Lichtensteiger
W
W
van Loveren
H
H
D000818:Animals; D000909:Antibodies, Helminth / Q000187:drug effects / Q000276:immunology; D003975:Diazepam / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005865:Gestational Age; D007107:Immune System / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017160:Trichinella spiralis / Q000187:drug effects* / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology*
D000909:Antibodies, Helminth; D003975:Diazepam