Differential effects of IL-1 beta and ibuprofen after endotoxic challenge in mice.

Interleukin-1 (IL-1) and ibuprofen modulate the host response in different models after endotoxic challenge. A comparative study was made between the two drugs, as they were jointly administered, to explore a potentiation of their therapeutic effects. Endotoxic challenge was provoked 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 administered 1 hr before and 30 min after the septic challenge. Serum levels of IL-1 alpha, tumor necrosis factor-alpha (TNF alpha), and interleukin-6 (IL-6) were determined 1,2, and 4 hr, post-LPS, and prostaglandin E2 (PGE2) urine levels 4,8, and 12 hr post-LPS, and a comparative mortality study was performed. IL-1 beta treatment provoked a reduction of IL-1 alpha, TNF alpha, and IL-6 without affecting PGE2, while ibuprofen provoked a later increase of IL-1 alpha, TNF alpha, and IL-6, with a decrease of PGE2. Both drugs caused a notable enhancement of survival, with no difference between them, but their combined administration caused no improvement. We conclude that both drugs exert a similar therapeutic effect in endotoxic shock by different mechanisms.