Platonin Improves Survival of Skin Allografts

Background. Platonin is an inrununomodulator with NF-kappa B inhibitory activity. It not only inhibits interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha production in sepsis, but also attenuates heatstroke reactions. In addition, platonin redirects differentiation of dendritic cells toward an intermediate stage of maturation. The study was designed to examine whether platonin can reduce acute graft rejection. Materials and Methods. A C57BL/6 to BALB/c mice skin transplantation model was used. Platonin was given intraperitoneally to transplant recipients at various doses. Skin grafts were submitted to histologic analysis. NF-kappa B DNA binding activity and inducible nitric oxide synthase (iNOS) expression were determined in harvested draining lymph nodes. Leukocyte count, hepatic and renal functions were serially assessed. An array of serum cytokines was evaluated on d 1, 3, 5, and 7 after skin transplantation. Results. Platonin resulted in significantly prolonged skin allograft survival in a dose- and time-dependent manner. Histologic changes in the skin allografts paralleled the gross appearance of rejection. Serum cytokine analysis shows that platonin significantly suppressed the production of the proinflanunatory cytokines IL-6 and TNF-alpha. However, no significant changes occurred in the serum levels of Th1-type and Th2-type cytokines. NF-kappa B activity and iNOS expression were remarkably suppressed in draining lymph nodes. In terms of toxicity, there were no significant differences in body weight, leukocyte count, plasma alanine aminotransferase, or creatinine between the platonintreated and control groups. Conclusion. Platonin effectively prolongs skin allograft survival without major toxicity. (C) 2010 Elsevier Inc. All rights reserved.