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.
Mansilla-Roselló
A
A
Experimental Surgery Unit, Virgen de las Nieves Foundation, Granada, Spain.
Ferrón-Orihuela
J A
JA
Ruiz-Cabello
F
F
Garrote-Lara
D
D
Fernández-Mondéjar
E
E
Delgado-Carrasco
M L
ML
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D015232:Dinoprostone / Q000652:urine; D004347:Drug Interactions; D005260:Female; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology*; D007375:Interleukin-1 / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008808:Mice, Inbred CBA; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D007052:Ibuprofen