Cyclic Nucleotide Levels in Psoriatic and Normal Keratomed Epidermis

Abstract

Changes in the cyclic nucleotide modulation of the epidermis could be involved in the altered state psoriatic lesional tissue. Since several conflicting values for cyclic AMP levels in the diseased state have been reported and cyclic GMP levels have been determined in only a small number of psoriatic patients, we have attempted to define the changes in epidermal cyclic nucleotide levels that can occur between psoriatic and normal epidermis. In this study, 34 normal volunteers and 28 persons with classical psoriasis vulgaris were biopsied using a Castroviejo keratome. The cyclic AMP and cyclic GMP levels of the snap frozen sample, which consists almost entirely of epidermal tissue, were determined by acetylated RIA of partially purified cyclic nucleotide fractions obtained by ion-exchange chromatography. The results indicate that cyclic GMP levels are increased 132% (NDA date base) in the lesional tissue when compared to the uninvolved areas. This is in agreement with our previously reported values obtained from a small number of biopsies. However, in contrast to our previous work, no decrease in lesional cyclic AMP in comparison with uninvolved epidermis was detected, although the content of cyclic AMP in all psoriatic tissue (both involved and uninvolved) was now observed to be decreased when compared to the normal values that have been obtained in our past and this present study. We conclude that cyclic AMP and cyclic GMP assays of biopsied epidermal tissue obtained form a large and varied human population can only suggest the involvement of cyclic nucleotides in the pathophysiology of the disease. Other systems and techniques are presently being used and developed to define the role of cyclic nucleotides in epidermal function and to formulate hypothesis on which to base further investigations of the misregulation of cyclic AMP and cyclic GMP in psoriatic tissue.