Using a zymosan-induced air pouch type inflammation model in rats, effects of dexamethasone, indomethacin and AA-861 on vascular permeability during a period of 30-60 min after the zymosan challenge and levels of prostaglandin (PG) E2 and peptide leukotrienes (LTs) in the pouch fluid were examined in order to get further insight into a mechanism of anti-inflammatory action of glucocorticoids. At this period, levels of peptide LTs, PGE2 and histamine in the pouch fluid were high.
Although AA-861 suppressed LTs production, only a weak but significant suppression of vascular permeability was obtained. PGE2 production was also inhibited dosedependently by AA-861. Indomethacin treatment inhibited both PGE2 production and vascular permeability response without affecting peptide LTs production. Consequently, inhibition of vascular permeability by AA-861 might be due to the inhibition of PGE2 production. Steroidal anti-inflammatory drug dexamethasone which had been injected subcutaneously 3 hr prior to the zymosan challenge, inhibited both PGE2 and peptide LT production. Although the inhibitory effect by dexamethasone of arachidonate metabolites production was not so potent as AA-861 and indomethacin, vascular permeability response was strongly suppressed. Combined treatment with indomethacin, pyrilamine and methysergide almost completely suppressed the vascular permeability response suggesting that histamine and serotonin released from subcutaneous mast cells are partly responsible for the vascular permeability increase. Dexamethasone treatment suppressed the vascular permeability without affecting histamine release.
These results indicate that some other mechanisms than the inhibition of arachidonate metabolism underlie for the anti-inflammatory action of the steroid.
