DIFFERENTIAL-EFFECTS OF PREDNISOLONE AND INDOMETHACIN ON ZYMOSAN-INDUCED INFLAMMATION IN A MODIFIED MURINE TISSUE-CHAMBER MODEL

A tissue-chamber model of inflammation in mice has been modified and u sed to investigate the kinetics of zymosan-induced inflammatory mediat ors such as tumour necrosis factor alpha (TNF alpha), interleukin-1 be ta(IL-1 beta) and prostaglandin E(2) (PGE(2)). 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 peak concentrations at 3 and 6h respectively after zymosan in jection. Intermediate high concentrations of IL-1 beta were observed u ntil the end of the experiment at 72 h, but TNF alpha concentrations d ecreased from 24 h to biologically insignificant values. In contrast, exudate PGE(2) and MPO activity increased up to 24h after zymosan inje ction and remained high until 72 h. At 6h after zymosan challenge, ora l pre-treatment with prednisolone (3 to 30mg/kg) dose-dependently redu ced TNF alpha IL-1 beta and PGE(2) concentrations while indomethacin ( 0.3 to 3 mg/kg) significantly attenuated PGE(2), slightly enhanced TNF alpha and had no effect on IL-1 beta concentrations in the exudate. B oth drugs had similar potencies against exudate and tissue MPO activit ies. Prednisolone inhibited IL-1 beta at 72 h post-zymosan. Indomethac in was more potent than prednisolone against PGE(2) (ID50 of <0.3 vers us 0.6mg/kg). The data obtained confirm the usefulness and reliability of this model in evaluating the effects of anti-inflammatory agents o n inflammatory mediators induced by zymosan.