THE EFFECTS OF THYMOPENTIN ON THE DEVELOPMENT OF SLE-LIKE SYNDROME INTHE MRL LPR-LPR MOUSE/

Thymopentin (TP-5) is a synthetic pentapeptide that corresponds to the active 32-36 amino acid sequence of the thymic hormone thymopoietin, of which it retains all the immunomodulatory properties. In this study , we have evaluated the effects of long term prophylactic treatment wi th TP-5 on the clinical, immunological and histological parameters of the SLE-like syndrome that spontaneously occurs in MRL/lpr-lpr (MRL-lp r) mice. TP-5, administered (s.c.) to these mice at the doses of 1, 10 and 100 mg/kg, was given daily, five times a week, from the 9th to th e 26th weeks of life. The prophylactic treatment with TP-5 prolonged i n a clear dose-dependent fashion the lifespan of MRL-lpr mice as compa red with PBS-treated control mice, and the effect reached statistical significance at the doses of 10 and 100 mg/kg. In parallel ex vivo stu dies, this clinical effect was associated with multiple profound modif ications of the immune system including: (i) the reduction of the spon taneous and Con A-induced release of interleukin-4 (IL-4); (ii) the in creased secretion of interferon-gamma (IFN-gamma) and IL-6 upon polycl onal mitogenic stimulation, and (iii) the amelioration of the defectiv e Con A-induced lympho-proliferative response. In contrast, although t he drug diminished the severity of proteinuria in MRL-lpr mice, it nei ther reduced histological signs of lupus nephritis nor diminished the serum titres of anti-native DNA and anti-histone autoantibodies. These results indicate that TP-5 displayed powerful immunomodulatory activi ties in a well known model of human SLE.