Celecoxib plays a multiple role to peripheral blood lymphocytes and allografts in acute rejection in rats after cardiac transplantation

Chin Med J (Engl). 2009 Jan 20;122(2):188-92.

Abstract

Background: Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug used as an adjuvant to sensitize cancer cells to apoptosis. However, in rats suffering from acute rejection, celecoxib reduced apoptosis of myocardial cells. We hypothesize that celecoxib reduces myocardial apoptosis either by inducing apoptosis in peripheral blood lymphocytes (PBLs) or by altering the percentage of CD4(+) and CD8(+) lymphocytes.

Methods: After cardiac transplantation, rats were administered intragastrically with celecoxib (50 mg/kg per day) for 3, 5 or 7 days, at which time the graft was excised and evaluated for organ rejection. In addition, PBLs were isolated from the blood to determine PBLs apoptosis, and the percentage of CD4(+) and CD8(+) lymphocytes.

Results: Celecoxib induced PBLs apoptosis in 3 days, but protected the cells from apoptosis at 5 and 7 days. Also, the percentage of CD4(+) lymphocytes decreased only at 3 days, but a reduction in the percentage of CD8(+) lymphocytes was not seen until 7 days after the transplant surgery. Celecoxib only decreased acute rejection at 5 days, with no discernible difference in rejection after 3 and 7 days.

Conclusions: The results suggested that celecoxib displayed a multiple physiological function in a time-dependent manner.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Celecoxib
  • Cells, Cultured
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control*
  • Heart Transplantation / immunology*
  • Lymphocytes / cytology
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Sulfonamides / pharmacology*
  • Transplantation, Homologous / immunology*

Substances

  • Anti-Inflammatory Agents
  • Pyrazoles
  • Sulfonamides
  • Celecoxib