DIFFERENTIAL-EFFECTS OF IL-1-BETA AND IBUPROFEN AFTER ENDOTOXIC CHALLENGE IN MICE

Interleukin-1 (IL-1) and ibuprofen modulate the host response in diffe rent models after endotoxic challenge. A comparative study was made be tween the two drugs, as they were jointly administered, to explore a p otentiation of their therapeutic effects. Endotoxic challenge was prov oked in CBA/H mice with lipopolysaccharide (LPS) from Escherichia coli (125 mg/kg), with administration of recombinant murine IL-1 beta (80 ng/mouse) 24 hr pre-LPS. Two doses of ibuprofen (1 mg/kg) were adminis tered 1 hr before and 30 min after the septic challenge. Serum levels of IL-1 alpha, tumor necrosis factor-alpha (TNF alpha), and interleuki n-6 (IL-6) were determined 1,2, and 4 hr, post-LPS, and prostaglandin E(2) (PGE(2)) urine levels 4,8, and 12 hr post-LPS, and a comparative mortality study was performed. IL-1 beta treatment provoked a reductio n of IL-1 alpha, TNF alpha, and IL-6 without affecting PGE(2), while i buprofen provoked a later increase of IL-1 alpha, TNF alpha, and IL-6, with a decrease of PGE(2). Both drugs caused a notable enhancement of survival, with no difference between them, but their combined adminis tration caused no improvement. We conclude that both drugs exert a sim ilar therapeutic effect in endotoxic shock by different mechanisms. (C ) 1997 Academic Press.