EFFECTS OF SPHINOGOSINE, ISOQUINOLINE AND TANNIC-ACID ON THE HUMAN TAPE-STRIPPING MODEL AND THE PSORIATIC LESION

Published data (mainly from rodent skin) suggest a correlation between compounds which inhibit protein kinase C (PKC), have anti-inflammator y or antitumor characteristics and possess antipsoriatic potential. We have investigated the effects of topical application of sphingosine ( a naturally occurring PKC inhibitor), isoquinoline (a component of coa l tar which showed antipsoriatic capacities in the mouse tail model) a nd tannic acid (a plant phenol with antitumor activity) on human skin. In each case we have assessed (a) the level of induction of ornithine decarboxylase (ODC) following Sellotape(R) stripping as an indicator for potential PKC inhibition in vivo, and (b) its effects on the lesio ns of chronic plaque psoriasis. The control group consisted of 18 heal thy volunteers, used for the ODC induction experiments (0.0/0.1/0.2 M sphingosine in ethanol, 100% coal tar and 0/50 mM tannic acid in aceto ne) and 17 psoriatic patients used for double-blind scoring of two ran domly selected lesions (0.0/0.1 M sphingosine in ethanol, 0.0/0.2% iso quinoline in white vaseline/lanette wax cream 50%/50% and 0/10% tannic acid in lanette wax cream) and also for some of the ODC induction exp eriments (0.0/0.2% isoquinoline and 0/10% tannic acid). Biopsies were taken 8 h after stripping and ODC activity was assessed by measurement of (CO2)-C-14 release. Lesions were scored with a modified psoriasis area and severity index on days 0,7 (isoquinoline and tannic acid), 13 (sphingosine) and 21 (isoquinoline and tannic acid). Application of 0 .1 or 0.2 M sphingosine resulted in a decrease of ODC activity of 52% and 66%, respectively (p < 0.01), but histologic sections showed intra epidermal necrosis. Isoquinoline, coal tar and tannic acid did not hav e any significant influence on ODC induction (p < 0.05). All compounds failed to show significant improvement of the psoriatic lesions. Ther efore we may conclude that 'theoretical' antipsoriatic agents may be l imited in practice by cytotoxicity and hence a narrow therapeutic inde x, poor penetration and lack of specificity. Further, a marked differe nce between the effects of these compounds on the skin of different sp ecies increases the difficulty of predicting antipsoriatic activity.