Dexamethasone and indomethacin treatment during endotoxicosis in the suckling rat

Gram negative sepsis/septic shock continues to be a major cause of morbidity and mortality in newborns. We studied the effects of anti-inflammatory drugs, indomethacin (IND) and dexamethasone (DX), on glucoregulation, body weight, and mortality in 10-day-old suckling rats administered Salmonella enteritidis lipopolysaccharide (LPS). IND (1.5 mg/kg) or DX (4 mg/kg) was intraperitoneally (ip) administered immediately after highly lethal LPS injection. Both IND and DX attenuated the LPS-induced hypoglycemia and lactacidemia, and decreased the mortality, IND did not alter body weight changes in rats with septic shock. DX continued a catabolic state and reduced their body weights. In rats fasted for 24 hr before LPS injection, DX, but not IND, increased the mortality. We concluded that IND and DX improved the LPS-induced glucose dyshomeostasis and decreased the mortality of endotoxic shock in 4-hr-fasted 10-day-old rats. Per contra, DX was detrimental in 24-hr-fasted 10-day-old endotoxic rats.