Differential effects of prednisolone and indomethacin on zymosan-induced inflammation in a modified murine tissue-chamber model.

Abstract

A tissue-chamber model of inflammation in mice has been modified and used to investigate the kinetics of zymosan-induced inflammatory mediators such as tumour necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2). In addition, the influx of polymorphonuclear leukocytes (PMN) into the chamber fluid and the granuloma surrounding the chamber was measured by myeloperoxidase (MPO) activity using a new microtitre plate assay. TNF alpha and IL-1 beta reached a peak concentrations at 3 and 6 h respectively after zymosan injection. Intermediate high concentrations of IL-1 beta were observed until the end of the experiment at 72 h, but TNF alpha concentrations decreased from 24 h to biologically insignificant values. In contrast, exudate PGE2 and MPO activity increased up to 24 h after zymosan injection and remained high until 72 h. At 6 h after zymosan challenge, oral pre-treatment with prednisolone (3 to 30 mg/kg) dose-dependently reduced TNF alpha, IL-1 beta and PGE2 concentrations while indomethacin (0.3 to 3 mg/kg) significantly attenuated PGE2, slightly enhanced TNF alpha and had no effect on IL-1 beta concentrations in the exudate. Both drugs had similar potencies against exudate and tissue MPO activities. Prednisolone inhibited IL-1 beta at 72 h post-zymosan. Indomethacin was more potent than prednisolone against PGE2 (ID50 of< 0.3 versus 0.6 mg/kg). The data obtained confirm the usefulness and reliability of this model in evaluating the effects of anti-inflammatory agents on inflammatory mediators induced by zymosan.