Local anti-inflammatory activities of tixocortol 21-pivalate, inhibition of prostaglandins and leukotrienes synthesis, in carrageenin-induced pleurisy. Reversion of effects by RU 486.

Since a direct effect of tixocortol pivalate (TP) has been described on cyclooxygenase pathway, local anti-inflammatory activities of some 21 thiol derivatives of steroids were investigated on the carrageenin-induced pleurisy model in comparison with dexamethasone (Dex) or other anti-inflammatory drugs. LTC4/D4 contents in pleural fluid were assayed by RIA as well as PGE2 levels to characterize the effects on arachidonate pathways. After oral administration, TP was inactive up to 1 g/kg on exudate volume and leukocyte migration as expected for this strict local anti-inflammatory steroid contrary to Dex (ID50 = 0.

Direct inhibition of cyclooxygenase pathway in platelets by tixocortol 21-pivalate: comparison with related structures, steroidal and non steroidal anti-inflammatory drugs.

Direct activity of the local anti-inflammatory steroid, tixocortol 21-pivalate (21 thioester derivative of cortisol) on metabolism of exogenous arachidonate by rabbit platelets was investigated in vitro. Tixocortol 21-pivalate inhibited generation of prostanoids from cyclooxygenase with an IC50 value of 19.6 microM without affecting the 12-lipoxygenase pathway.

The presence of lipocortin in human embryonic skin fibroblasts and its regulation by anti-inflammatory steroids.

Human embryonic skin fibroblasts in culture produce pro-inflammatory lipid mediators and all types of prostanoids. When these cells were treated with the anti-inflammatory steroid, dexamethasone, prostaglandin production was inhibited. This phenomenon required glucocorticoid receptor occupancy and mRNA and protein synthesis.