Abstract | BACKGROUND: Inhibition of cyclooxygenase-2 with a reduction of prostaglandin E(2)production by the specific antagonist NS-398 has been shown to have beneficial effects on immune function and survival in a trauma model. Immune function after experimental hemorrhagic shock and subsequent sepsis may be gender-related, with enhanced immunity and better survival in females. However, it remains unclear if the observed effect of NS-398 treatment is gender-related following hemorrhagic shock and subsequent sepsis. METHODS: Male and female CBA/J mice (age: 2-3 months) were subjected to hemorrhagic shock (35 +/- 5 mm Hg for 90 min and fluid resuscitation) or sham operation. At resuscitation and after 20 and 40 h each received either NS-398 10 mg/kg or placebo i.p. At 48 h after resuscitation, either splenocytes and peritoneal macrophages (pM phi) were harvested (n = 8 per group), or polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Following CLP, either 10-day survival (n = 15 per group) was determined or pM phi and splenocytes were harvested 4 h after CLP (n = 8 per group). Cytokine release of pM phi, and splenocyte proliferation and responsiveness in vitro were assessed. RESULTS: Treatment with NS-398 led to lower PGE(2) levels as compared to placebo-treated animals, reaching significance (p < 0.05) in males. Placebo-treated males had significantly depressed proinflammatory immune response (IL-1, IL-6, IL-2, IFN-gamma) after hemorrhagic shock and experienced further suppression by CLP (all, p < 0.05). In contrast, young females displayed unchanged cytokine release after hemorrhagic shock, but a comparable suppression following CLP. Treatment with NS-398 did not influence cytokine release nor survival. CONCLUSIONS: Despite a significant reduction of PGE(2) concentration, NS-398 treatment has no beneficial effects on cytokine release and survival in this model of hemorrhage and subsequent sepsis.
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Authors | Volker Kahlke, Mirja Seidel, Sietje Stapela, Kerstin Brötzmann, Clemens Schafmayer, Jörg Schröder |
Journal | Surgical infections
(Surg Infect (Larchmt))
Vol. 5
Issue 1
Pg. 29-37
( 2004)
ISSN: 1096-2964 [Print] United States |
PMID | 15142421
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Cyclooxygenase 2 Inhibitors
- Cyclooxygenase Inhibitors
- Cytokines
- Isoenzymes
- Nitrobenzenes
- Sulfonamides
- N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
- Cyclooxygenase 2
- Prostaglandin-Endoperoxide Synthases
- Dinoprostone
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Topics |
- Animals
- Cyclooxygenase 2
- Cyclooxygenase 2 Inhibitors
- Cyclooxygenase Inhibitors
(pharmacology)
- Cytokines
(drug effects, metabolism)
- Dinoprostone
(analysis, metabolism)
- Disease Models, Animal
- Female
- Injections, Intraperitoneal
- Isoenzymes
(metabolism)
- Male
- Mice
- Mice, Inbred CBA
- Nitrobenzenes
(pharmacology)
- Probability
- Prostaglandin-Endoperoxide Synthases
(metabolism)
- Reference Values
- Sensitivity and Specificity
- Sepsis
(drug therapy, mortality)
- Sex Factors
- Shock, Hemorrhagic
(drug therapy, mortality)
- Sulfonamides
(pharmacology)
- Survival Analysis
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