Effects of pidotimod on the immune and the neuroendocrine system in the aging rat

The effects of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a synthetic thymic dipeptide, on immune response in 2 and 24 month-old rats were investigated. Peripheral blood lymphocytes and splenocytes of aging rats treated for 1 week with different doses of pidotimod showed increased rates of mitogen-stimulated proliferation. Also, interleukin-2 production by 24 month-old rat lymphocytes was significantly increased after treatment with the drug. In addition, the response of the hypothalamic-pituitary-adrenal (HPA) axis to interleukin-1 in 2 and 24 month-old Sprague-Dawley rats previously treated with pidotimod was studies. Blood samples were withdrawn--30, 0, 30, 60, 90 and 120 min after interleukin-1 injection. Interleukin-1 injection stimulated ACTH secretion in a dose-related manner, in both 2 and 24 month-old rats. Peak of the effect was 60 min after the injection. ACTH levels returned to baseline within 120 min in 2 month-old rats, whereas they were still high in untreated 24 month-old rats. However, plasma ACTH levels at 120 min were significantly lower in 24 month-old rats treated with pidotimod. Results suggest that pidotimod possesses immunomodulating properties, such as enhancement of splenocyte and peripheral blood lymphocyte proliferation, and improvement of the deficitary feedback mechanism between the hypothalamic-pituitary-adrenal axis and cytokines and, namely, interleukin-1 in the aging rat.