Pr. Elford et al., REDUCTION OF INFLAMMATION AND PYREXIA IN THE RAT BY ORAL-ADMINISTRATION OF SDZ-224-015, AN INHIBITOR OF THE INTERLEUKIN-1-BETA CONVERTING-ENZYME, British Journal of Pharmacology, 115(4), 1995, pp. 601-606
1 The aim of this study was to determine whether a synthetic inhibitor
of the interleukin-lp converting enzyme (ICE) displays oral activity
in models of inflammation. 2 To this end, the ICE inhibitor, SDZ 224-0
15, was examined in rat paw oedema, pyrexia and nociception tests. 3 S
DZ 224-015 (0.3-300 mu g kg(-1)) potently reduced carrageenin-induced
paw oedema, with an oral ED(50) of approximately 25 mu g kg(-1). This
effect was independent of endogenous glucocorticoid, as shown by reten
tion of activity upon adrenalectomy. 4 Pyrexia induced by lipopolysacc
haride (0.1 mg kg(-1) s.c.) or by interleukin-1 beta (100 ng i.v.) was
also reduced, over a similar dose-range to oedema (oral ED(50)s 11 mu
g kg(-1) and 4 mu g kg(-1) respectively). 5 SDZ 224-015 (0.2-5 mg kg(
-1), p.o.) displayed analgesic activity in the Randall-Selitto yeast-i
nflamed paw pressure test, significant at a dose of 1 mg kg(-1) p.o. 6
Thus, SDZ 224-015 has potent oral activity in several acute models fo
r inflammation, suggesting that ICE inhibitors may constitute a novel
type of anti-inflammatory agent.