Platonin improves survival of skin allografts.
BACKGROUND
Platonin is an immunomodulator with NF-κB inhibitory activity. It not only inhibits interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α 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.


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-κB 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 proinflammatory cytokines IL-6 and TNF-α. However, no significant changes occurred in the serum levels of Th1-type and Th2-type cytokines. NF-κB 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 platonin-treated and control groups.


CONCLUSIONS
Platonin effectively prolongs skin allograft survival without major toxicity.
Cheng
Shih-Ping
SP
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Lee
Jie-Jen
JJ
Chi
Chin-Wen
CW
Chang
Kuo-Ming
KM
Chen
Yu-Jen
YJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D016038:Skin Transplantation / Q000276:immunology*; D013844:Thiazoles / Q000494:pharmacology* / Q000633:toxicity; D014184:Transplantation, Homologous
D016207:Cytokines; D007155:Immunologic Factors; D016328:NF-kappa B; D013844:Thiazoles; C032149:platonin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse