Alterations in interleukin-6 production by LPS- and Con A-stimulated mixed splenocytes, spleen macrophages and lymphocytes in prenatally diazepam-exposed rats.
Prenatal exposure to diazepam leads to a suppression of mitogen or allogen-induced lymphocyte proliferation as well as to a reduced production of tumour necrosis factor (TNF)-alpha from rat splenocytes during postnatal development of rats. We analysed the secretion of interleukin (IL)-6 which occurs at a later stage of the cytokine cascade. Splenocytes of male offspring from Long Evans rats, treated with a daily dose of diazepam (1.25 mg/kg) from gestational day 14 to 20, were stimulated with lipopolysaccharide (LPS) and concanavalin A (Con A). In response to LPS, IL-6 liberation was significantly lower in mixed splenocytes and spleen macrophages of 2 and 8 week old prenatally diazepam-treated rats than in controls. Spleen lymphocyte preparations of prenatally treated animals exhibited a reduction of IL-6 release at 12 h and an increase at 24 h of incubation. At 2 weeks of age, Con A-induced IL-6 production could only be detected in mixed splenocytes; prenatally treated rats were releasing significantly less IL-6 than controls. In 8 week old rats, IL-6 liberation from mixed splenocytes and spleen macrophages was significantly lower in prenatally treated animals than in controls. Spleen lymphocytes presented a complex response picture depending upon incubation conditions. Our data indicate that in prenatally diazepam-exposed rats, the disturbance of cytokine release also extends to cytokines which play an important role in the later phases of immune responses.
Schreiber
A A
AA
Institute of Pharmacology, University of Zurich, Switzerland.
Frei
K
K
Lichtensteiger
W
W
Schlumpf
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D008070:Lipopolysaccharides; D003208:Concanavalin A; D003975:Diazepam