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 i nvestigated. Peripheral blood lymphocytes and splenocytes of aging rat s treated for 1 week with different doses of pidotimod showed increase d rates of mitogen-stimulated proliferation. Also, interleukin-2 produ ction by 24 month-old rat lymphocytes was significantly increased afte r treatment with the drug. In addition, the response of the hypothalam ic-pituitary-adrenal (HPA) axis to interleukin-1 in 2 and 24 month-old Sprague-Dawley rats previously treated with pidotimod was studies. Bl ood samples were withdrawn - 30, 0, 30, 60; 90 and 120 min after inter leukin-1 injection Interleukin-1 injection stimulated ACTH secretion i n a dose-related manner, in both 2 and 24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 u ntreated 24 month-old rats. However, plasma ACTH levels at 120 min wer e significantly lower in 24 month-old rats treated with pidotimod. Res ults suggest that pidotimod possesses immunomodulating properties, suc h as enhancement of splenocyte and peripheral blood lymphocyte prolife ration, and improvement of the deficitary feedback mechanisms between the hypothalamic-pituitary-adrenal axis and cytokines and, namely, int erleukin-1 in the aging rat.