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KMID : 0361120120260040248
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Korean Journal of Transplantation
2012 Volume.26 No. 4 p.248 ~ p.253
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Changes in Serum Cytokine Profile after AEB071 (Sotrastaurin) or Tacrolimus versus Their Combinations in Rat Heterotopic Cardiac Allografts
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Joo Dong-Jin
Fang Yu-Hui
Huh Kyu-Ha
Kim Myoung-Soo
Suh Hwal
Kim Yu-Seun
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Abstract
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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)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF)-α 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-γ, 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-γ, IL-4, IL-6, and TNF-α.
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.
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KEYWORD
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Sotrastaurin, Cytokines, Heart transplantation, Immunosuppression, Tacrolimus
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