| Autor: |
Strong, Vivian E. Mack, Mackrell, Peter J., Concannon, Erin M., Naama, Hassan A., Schaefer, Peter A., Shaftan, Gerald W., Stapleton, Philip P., Daly, John M. |
| Zdroj: |
Shock; September 2000, Vol. 14 Issue: 3 p374-379, 6p |
| Abstrakt: |
Major injury leads to impaired immune responses and increases the risk of infectious complications. Following trauma, increased prostaglandin E2PGE2levels may be important in immunodysregulation. We hypothesized that blocking PGE2with NS398, a selective COX2 inhibitor, during the first 24 h after injury may modify the immune response and protect the host from a subsequent septic challenge. BALBc mice were given NS398 10mgkg immediately after injury, at 12, and at 24 h after sham injury or trauma femur fracture and 40 hemorrhage. On day 7 after injury, splenic macrophages were evaluated for cytokine production and COX2 mRNA. In a separate study mice were injured, then given 3 doses of NS398. After 7 days, cecal ligation and puncture was performed and mice were followed for survival. Traumatized mice given NS398 had a significant survival advantage compared with trauma mice alone P< 0.001. Macrophages from traumatized mice showed increased COX2 mRNA and proinflammatory cytokines compared with controls P< 0.05, whereas treatment of injured mice with NS398 significantly decreased proinflammatory cytokine production P< 0.05 and COX2 mRNA. Therefore NS398 given within 24 h of injury suppressed PGE2through inhibition of cyclooxygenase, in addition to decreasing proinflammatory cytokines, and providing a survival advantage to the host. |
| Databáze: |
Supplemental Index |
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