[Re-evaluation of the carrageenin-induced abscess model as a screening method for anti-inflammatory agents]

For the simple assay of anti-inflammatory agents and the analysis of their mode of action, the early inflammatory reactions of the carrageenin abscess model in rats were studied by determining abscess (exudate) weight, vascular permeability measured by extravascular dye leakage, protein, prostaglandins (PGs), and DNA (an index of leucocyte infiltration). Subcutaneous injection of 0.5 ml of 2% carrageenin in the dorsal sacral region of rats induced an edema with an initial weak phase (3 hr) followed by a second pronounced phase, reaching a maximum (2.3 g) at 15 hr and declining steadily thereafter. During the first 15 hr, there was a good correlation between the edema formation and changes in the increased vascular permeability, and also the PGE contents in the exudate paralleled the permeability, but thereafter, these components did not follow the same time course. The marked increase in DNA content in the exudate started after a lag time of a few hr in correspondence with the second accelerated edema formation. The edema formation was effectively inhibited by indomethacin and dexamethasone given simultaneously with the irritant injection; maximum inhibition with indomethacin (2 mg/kg, p.o.) was 36% at 15 hr and 48% with dexamethasone (0.1 mg/kg, p.o.) at 9 hr. Indomethacin very significantly affected exudate PGE levels and vascular permeability, rather than suppressing the edema formation. When the treatment was initiated at 9 hr after injury, it was not effective in reducing the weight of the 24-hr abscess, whereas it had significant effect on the PGE concentration. Dexamethasone did not exert significant effect on the PGE levels despite its potent and steady anti-edematous activities.(ABSTRACT TRUNCATED AT 250 WORDS)