Changes in Serum Cytokine Profile after AEB071 (Sotrastaurin) or Tacrolimus versus Their Combinations in Rat Heterotopic Cardiac Allografts.
10.4285/jkstn.2012.26.4.248
- Author:
Dong Jin JOO
1
;
Yu Hui FANG
;
Kyu Ha HUH
;
Myoung Soo KIM
;
Hwal SUH
;
Yu Seun KIM
Author Information
1. The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea. yukim@yuhs.ac
- Publication Type:Original Article
- Keywords:
Sotrastaurin;
Cytokines;
Heart transplantation;
Immunosuppression;
Tacrolimus
- MeSH:
Animals;
Cytokines;
Heart Transplantation;
Immunosuppression;
Interferons;
Interleukin-10;
Interleukin-2;
Interleukin-4;
Interleukin-6;
Interleukins;
Pyrroles;
Quinazolines;
Rats;
Rejection (Psychology);
Rodentia;
Tacrolimus;
Transplantation, Homologous;
Transplants;
Tumor Necrosis Factor-alpha
- From:The Journal of the Korean Society for Transplantation
2012;26(4):248-253
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: AEB071, an orally available PKC inhibitor, prevents organ rejection after transplantation in rodents and man. Furthermore, pro-inflammatory cytokines and inflammatory processes are important mediators of transplanted organ rejection. We therefore examined whether single or combination therapies of AEB071 and/or tacrolimus affect cytokine profiles in a rat cardiac allograft model. METHODS: AEB071 (60 mg/kg twice a day) and tacrolimus (0.6 or 1.2 mg/kg once a day) were orally administered daily after cardiac transplantation. Interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF)-alpha levels in serum were subsequently measured 5 days after cardiac transplantation using a multiplex protein assay system. RESULTS: All cytokine levels were significantly depressed in cardiac transplanted rats treated with AEB071, whereas tacrolimus only reduced IFN-gamma, IL-2, IL-4, IL-6, and IL-10 levels. When administered in combination, AEB071 and low- or high-dose tacrolimus had additive effects on IFN-gamma, IL-4, IL-6, and TNF-alpha. CONCLUSIONS: These results suggest that AEB071 inhibits T cell activation by blocking the production of proinflammatory cytokines, and that tacrolimus combined with AEB071 can effectively regulate inflammatory cytokines in the transplantation setting.
