The six-day-old rat air pouch model of inflammation: characterization of the inflammatory response to carrageenan.
Inflammation was induced in the 6-day-old rat air pouch by injection of carrageenan. The model was characterized in terms of exudate volume, leucocyte influx, cell free protein, prostaglandin E2 levels, and granuloma formation. The time course of all these inflammatory markers, except prostaglandin E2, showed a 3-hr lag followed by a rapid increase to 8 hr. Thereafter, the rate of increase was much slower to 48 hr. Differential cell counts indicated a predominantly polymorphonuclear cell response (75%) during the first 48 hr. Prostaglandin E2 levels increased rapidly after a 3-hr lag, to a maximum of 440 +/- 140 ng/mL at 15 hr and thereafter quickly declined to 140 +/- 60 ng/mL at 21 hr. Prostaglandin E2 levels were the most sensitive inflammatory marker to (S+)-ibuprofen and were reduced dose dependently in the range 0.05 to 1 mg/kg. We have demonstrated the time course for duration of NSAID-induced reduction of prostaglandin E2 levels during inflammation in an individual animal. Rac-ibuprofen (0.1-1 mg/kg) reduced leucocyte influx at 3 and 5 hr, after which drug effects gradually diminished by 24 hr. Rac-ibuprofen at 1 mg/kg significantly reduced the volume of air pouch exudate recovered at 24 hr but had no effect on protein levels.
Department of Pharmacy, University of Manchester, England, United Kingdom.
S W
SW
Martin
A J
AJ
Stevens
B S
BS
Brennan
D
D
Davies
M
M
Rowland
J B
JB
Houston
D000818:Animals; D002351:Carrageenan; D015232:Dinoprostone / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005122:Exudates and Transudates / Q000737:chemistry / Q000187:drug effects; D006097:Granulation Tissue; D006099:Granuloma; D007052:Ibuprofen / Q000032:analysis / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced*; D007958:Leukocyte Count; D008297:Male; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D011506:Proteins; D002351:Carrageenan; D015232:Dinoprostone; D007052:Ibuprofen