Blockade of prostaglandin products augments macrophage and neutrophil tumor necrosis factor synthesis in burn injury

Yuan Lin Dong, David N. Herndon, Tina Z. Yan, J. Paul Waymack

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Cyclooxygenase products are believed to be a major regulator of host tumor necrosis factor-α (TNF-α) production in response to trauma and sepsis. To study this relationship, Lewis rats underwent a 30% burn or sham burn. Dimethyl-prostaglandin E (dPGE, 50 μg/kg), ibuprofen (IBU, 2 mg/kg), or saline was administered twice daily. Rats were sacrificed at Day 7 to obtain Kupffer cells, peritoneal macrophages, splenic macrophages, and neutrophils. For in vivo studies, 106 cells from each group were cultured with 10 μg of lipopolysaccharide (LPS). For in vitro studies, cells from the burn and sham groups were cultured with LPS and dPGE (10 μg/ml), IBU (10 μg/ml), or saline. The supernatants were harvested after 2, 6, and 24 hr of culture and assayed for TNF-α (μ/ml) by L929 cytolysis. Burn injury resulted in a significant increase in Kupffer cell and neutrophil TNF-α production compared to the sham group (P < 0.001, ANOVA). The administration of IBU to burned animals led to a pronounced elevation of TNF-α production by Kupffer cells, peritoneal macrophages, and neutrophils compared to vehicle-treated burned animals (P < 0.001, ANOVA). With in vitro studies, IBU increased Kupffer cell, peritoneal macrophage, and neutrophil TNF-α release by 213, 327, and 198%, respectively (P < 0.05, ANOVA). dPGE caused a marked decrease in Kupffer cell and peritoneal macrophage TNF-α synthesis by 50 and 43%, respectively (P <0.01, ANOVA). In conclusion, prostaglandins are critical for down regulating TNF-α production. Clinical use of cyclooxygenase inhibitors may result in adverse outcomes due to the excessive TNF-α production.

Original languageEnglish (US)
Pages (from-to)480-485
Number of pages6
JournalJournal of Surgical Research
Volume54
Issue number5
DOIs
StatePublished - May 1993

ASJC Scopus subject areas

  • Surgery

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