Cutaneous inflammation and proliferation in vitro: Differential effects and mode of action of topical glucocorticoids

The nonhalogenated double ester of prednisolone, prednicarbate (PC), is the first topical glucocorticoid with an improved benefit/risk ratio verified clinically and in vitro. To evaluate if this is due to unique characteristi cs of this steroid, a new compound created according to an identical concep t, prednisolone 17-ethylcarbonate, 21-phenylacetate (PEP), and the new halo genated monoester desoximetasone 21-cinnamate (DCE) were tested and compare d to PC, desoximetasone (DM) and betamethasone 17-valerate (BMV). Isolated foreskin keratinocytes served for in vitro investigations of anti-inflammat ory prospectively, Whereas PC and PEP inhibited 1 alpha and 11-6 production in fibroblasts only to a minor extent, cytokine synthesis was strongly aff ected by the conventional glucocorticoids BMV and DM, but also by DCE, The minor unwanted effect of PC and PEP on fibroblasts was also reflected by th eir low influence on cell proliferation as derived from H-3-thymidine incor poration. Again, more pronounced antiproliferative features were seen with the halogenated glucocorticolds, In the following, the correlation between antiphlogistic effects in keratinocytes (suppression of 11-1 alpha) and ant iproliferative effects in fibroblasts (suppression of Il-la and 11-6; 3H-th ymidine incorporation) was analyzed. Here, PC is revealed as the only gluco corticoid with an improved benefit/risk ratio. Native PEP is shown to be al most ineffective and DCE presents exactly the opposite features of PC. It i s tempting to speculate if this is due to different glucocorticoid receptor subtypes or different signaling pathways in keratinocytes and fibroblasts. Copyright (C) 2000 S.Karger AG, Basel.