Abstract
Background. Cyclooxygenase-2 (Cox-2), the inducible form of Cox, is a rate-limiting enzyme in
the synthesis of prostaglandins (PGs). Prostaglandin E2 (PGE2) and other eicosanoids possess immunosuppressive properties. Previously, traumatic
injury was found to stimulate the synthesis of PGs and cause immune dysfunction. In
this study a murine model was used to determine the effect of trauma on the expression
of Cox-2 in macrophages and to elucidate the role of Cox-2 in trauma-induced immune
dysfunction. Methods. Mice were randomized to control or trauma (femur fracture plus 40% blood volume hemorrhage)
groups. One, 4, and 7 days after injury, splenic macrophages were isolated and assayed
for expression of Cox-2 and production of PGE2. In addition, the effect of pharmacologically inhibiting Cox-2 or knocking out the
Cox-2 gene on trauma-induced suppression of splenocyte mitogenesis was determined. Results. Trauma led to increased expression of Cox-2, enhanced synthesis of PGE2, and suppressed splenocyte mitogenesis. Both pharmacologic inhibition and genetic
deletion of Cox-2 abrogated trauma-mediated suppression of splenocyte mitogenesis. Conclusions. These experiments link trauma-induced increases in Cox-2 expression and PGE2 production to reduced immune function. Cox-2 represents a potential pharmacologic
target to prevent or reverse trauma-induced immunosuppression. (Surgery 2001;130:826-33.)
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Article info
Publication history
Accepted:
April 21,
2001
Footnotes
*Supported by grants RO1 DK50201 (J.M.D.) and T32CA68971 from the National Institutes of Health.
**Reprint requests: John M. Daly, MD, New York Presbyterian Hospital, Department of Surgery, 525 East 68th St, Room F-739, New York, NY 10021.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
