Postburn metabolic and immunological alterations may in part be due to translocation of gut exotoxin and endotoxin, which can result in tumour necrosis factor (TNF) and prostaglandin E (PGE) production by macrophages. We evaluated the effect of burn injury, plus exotoxin and endotoxin on TNF-α and PGE production by Kupffer cells, and peritoneal macrophages. Adult Wistar rats underwent 30 per cent TBSA burn or sham burn. Kupffer cells were harvested from rat livers and peritoneal macrophages from the abdominal cavity 24 h postburn. They were cultured overnight at 1 × 106 cells/ml and stimulated with saline, 5 μg/ml of Pseud. aeruginosa Exotoxin A (Exo-A), 5 μg/ml of Pseud. aeruginosa Endotoxin (Endo), Exo-A + Endo, or Exo-A + Endo + the PGE derivative 16,16 dimethyl-PGE (dPGE) (10μg/ml). The supernatants were harvested after 4, 24 and 48 h of culture and assayed for TNF-α and PGE. Results showed that burn injury induced an increase in TNF-α and PGE production by Kupffer cells stimulated with Exo-A, Endo, and both Exo-A + Endo (P < 0.05). The release of TNF-α by Kupffer cells was downregulated by exogenous PGE (P < 0.05). The increased TNF-α production was inversely related to PGE levels. In conclusion, both burn injury and Exo-A potentiate the responsiveness of Kupffer cells and peritoneal macrophages to endotoxin as measured by the rate of production of TNF-α and PGE. PGE may locally downregulate the immune response by limiting Kupffer cells' and peritoneal macrophages' TNF-α production.
ASJC Scopus subject areas
- Emergency Medicine