NDLI: Reduction of inflammation and pyrexia in the rat by oral administration of SDZ 224-015, an inhibitor of the interleukin-1 beta converting enzyme.

Content Provider	PubMed Central
Author	Elford, P. R. Heng, R. Révész, L. Mackenzie, A. R.
Abstract	1. The aim of this study was to determine whether a synthetic inhibitor of the interleukin-1 beta converting enzyme (ICE) displays oral activity in models of inflammation. 2. To this end, the ICE inhibitor, SDZ 224-015, was examined in rat paw oedema, pyrexia and nociception tests. 3. SDZ 224-015 (0.3-300 micrograms kg-1) potently reduced carrageenin-induced paw oedema, with an oral ED50 of approximately 25 micrograms kg-1. This effect was independent of endogenous glucocorticoid, as shown by retention of activity upon adrenalectomy. 4. Pyrexia induced by lipopolysaccharide (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 ED50s 11 micrograms kg-1 and 4 micrograms kg-1 respectively). 5. SDZ 224-015 (0.2-5 mg kg-1, p.o.) displayed analgesic activity in the Randall-Selitto yeast-inflamed 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 for inflammation, suggesting that ICE inhibitors may constitute a novel type of anti-inflammatory agent.
Starting Page	601
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	4
Volume Number	115
Language	English
Publisher Date	1995-06-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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Reduction of inflammation and pyrexia in the rat by oral administration of SDZ 224-015, an inhibitor of the interleukin-1 beta converting enzyme.