EFFECTS OF MOMETASONE FUROATE ON HUMAN KERATINOCYTES AND FIBROBLASTS IN-VITRO

The long-term treatment of inflammatory skin diseases with topical glu cocorticoids is limited by their side effects such as skin atrophy, de layed wound healing and striae distensae. Mometasone furoate (MF) is a newly synthesized glucocorticoid with the advantage of increasing eff icacy and reducing the number of adverse effects. The aim of our study was to compare the effects of MF and conventional fluorinated cortico steroids on a human keratinocyte cell line (HaCat) and human skin fibr oblasts in vitro. Monolayer cultures of these cell lines were exposed to different concentrations of the active compounds for 5 days to anal yze the influence on morphology and proliferation. Chemotaxis of HaCat cells and fibroblasts was studied in blind-well Boyden chambers using collagen type I and fibroblast-conditioned medium as a chemoattractan t. Additionally, fibroblasts were used to investigate the contraction of collagen gels since lattice contraction appears to model the contra ction of skin wounds. All glucocorticoids tested influenced fibroblast and keratinocyte proliferation in a dose-dependent manner, yet the ef fect was clearly more marked with fluorinated corticosteroids than wit h MF. Similar effects were obtained using the chemotaxis assay. At low concentrations (10(-9) M) MF exerted almost no influence, while the c onventional fluorinated substances inhibited direct migration signific antly. Contraction of collagen gels was inhibited completely by betame thasone valerate at high concentrations (10(-5)-10(-3) M), but only pa rtially inhibited by MF at its highest concentration (10(-3) M). Altho ugh MF reveals high anti-inflammatory activity similar to that known f or conventional fluorinated derivatives of corticosteroids, the study shows that MF has less effect in the tested in vitro systems. Therefor e, it remains to be seen whether these data might indicate the possibi lity of a dissociation between the inflammatory activity and the inhib ition of the biosynthetic capacities of fibroblasts and keratinocytes by modification of the steroidal structure of corticosteroids.