Changes in Serum Cytokine Profile after AEB071 (Sotrastaurin) or Tacrolimus versus Their Combinations in Rat Heterotopic Cardiac Allografts / 대한이식학회지
The Journal of the Korean Society for Transplantation
;
: 248-253, 2012.
Article
in English
| WPRIM
| ID: wpr-127069
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pyrroles
/
Quinazolines
/
Rejection, Psychology
/
Rodentia
/
Transplantation, Homologous
/
Cytokines
/
Heart Transplantation
/
Immunosuppression Therapy
/
Interleukins
/
Interferons
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
The Journal of the Korean Society for Transplantation
Year:
2012
Type:
Article
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