THE EFFECT OF CYCLOSPORINE-A AND FK-506 ON THE CAMP CONTENT IN PSORIATIC KERATINOCYTES

FK 506 and cyclosporin A (CYA) are two immunosuppressive drugs which a re known to be effective in the treatment of psoriasis by inhibiting t he activation of T cells. In contrast, their influence on the prolifer ation of keratinocytes is discussed controversially. The second messen ger cyclic adenosine monophosphate (cAMP) has been regarded as a regul ator for cell growth and proliferation for 20 years. Hyperproliferatio n of many cells and particularly of psoriatic keratinocytes was specul ated to be due to a decrease in cAMP levels in the psoriatic epidermis , whereas new findings could not confirm these observations. To clarif y this discussion we determined the intracellular cAMP content in isop renaline-stimulated keratinocytes from psoriatics and controls after t reatment with CyA or FK 506. Ethanol and the beta-blocking drug propra nolol served as controls. The basal level of cAMP and the response to isoprenaline in psoriatic keratinocytes did not differ from those of c ontrols. CyA dramatically reduced the cAMP level and FK 506 just sligh tly diminished it in a dose-dependent manner, Both drugs diminished th e cAMP level more effectively in the keratinocytes from lesional psori atic skin than in keratinocytes from controls. These data provide evid ence that CyA influences early signal transduction pathways by depress ing the intracellular cAMP in keratinocytes, This supports the view of other groups that CyA and perhaps also FK 506 influence not only immu nocompetent cells but also keratinocytes in the treatment of psoriasis . Furthermore, it is doubtful that a low cAMP level is a positive regu lator for cell growth and the hyperproliferation of psoriatic keratino cytes.