ALTERATIONS IN INTERLEUKIN-6 PRODUCTION BY LPS-STIMULATED 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 all ogen-induced lymphocyte proliferation as well as to a reduced producti on of tumour necrosis factor (TNF)-alpha from rat splenocytes during p ostnatal development of rats. We analysed the secretion of interleukin (IL)-6 which occurs at a later stage of the cytokine cascade. Splenoc ytes 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 stimulat ed with lipopolysaccaride (LPS) and concanavalin A (Con A). In respons e to LPS, IL-6 liberation was significantly lower in mixed splenocytes and spleen macrophages of 2 and 8 week old prenatally diazepam-treate d rats than in controls. Spleen lymphocyte preparations of prenatally treated animals exhibited a reduction of IL-6 release at 12 h and an i ncrease at 24 h of incubation. At 2 weeks of age, Con A-induced IL-6 p roduction could only be detected in mixed splenocytes: prenatally trea ted rats were releasing significantly less IL-6 than controls. In 8 we ek old rats, IL-6 liberation from mixed splenocytes and spleen macroph ages was significantly lower in prenatally treated animals than in con trols. Spleen lymphocytes presented a complex response picture dependi ng upon incubation conditions. Our data indicate that in prenatally di azepam-exposed rats, the disturbance of cytokine release also extends to cytokines which play an important role in the later phases of immun e responses.