The new immunosuppressant PLNPK prolongs allograft survival in mice

Abstract

The pentapeptide PLNPK (Pro-Leu-Asn-Pro-Lys) is extracted from the spleen. Preliminary studies have shown that PLNPK could inhibit T lymphocyte transformation and antibody production. In the present study, we detected the inhibitory effect of PLNPK on one-way mixed leukocyte reaction (MLR) in vitro and observed the effect of PLNPK on the duration of allograft survival in mouse models of skin or cardiac transplantation. Pathological damage and T cell infiltration of the grafts were also detected. Results showed that PLNPK could significantly inhibit T lymphocyte proliferation, with an optimized inhibition of 40%. Also PLNPK could significantly prolong the mean survival time of skin allograft and cardiac allograft, producing survival rates of 42% and 38.7%, respectively. PLNPK at a dose of 200 μg/kg/d or 100 μg/kg/d could significantly suppress ConA-induced T cell proliferation and T cell IL-2 secretion in transplant recipient mice, compared to the saline group ( P < 0.05). This information suggests that PLNPK can effectively antagonize transplant rejection, possibly by reducing IL-2 secretion by T cells and inhibiting T cell proliferation and activation.