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Changes in Serum Cytokine Profile after AEB071 (Sotrastaurin) or Tacrolimus versus Their Combinations in Rat Heterotopic Cardiac Allografts.

Title
 Changes in Serum Cytokine Profile after AEB071 (Sotrastaurin) or Tacrolimus versus Their Combinations in Rat Heterotopic Cardiac Allografts. 
Authors
 Dong Jin Joo ; Yu Hui Fang ; Yu Seun Kim ; Hwal Suh ; Myoung Soo Kim ; Kyu Ha Huh 
Issue Date
2012
Journal Title
 대한이식학회지 
ISSN
 1598-1711 
Citation
 대한이식학회지, Vol.26(4) : 248~253, 2012 
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/92322
DOI
10.4285/jkstn.2012.26.4.248
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Medical Engineering
1. 연구논문 > 1. College of Medicine > Dept. of Surgery
Yonsei Authors
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