Cyclosporin A reduces skin collagen content in renal graft recipients

Stimulated by the observation of a direct cytopathic effect of cyclosporin A on dermal fibroblasts we have examined total skin collagen content and collagenase activity in three groups of patients. Group 1 (controls) consisted of 16 patients without internal diseases, group 2 of 12 patients with renal transplantation on cyclosporin A therapy and group 3 of six patients with renal transplantation on corticosteroid/azathioprine therapy.Total skin collagen was measured by hydroxyproline/protein determination, collagenase activity according to the principle of Wünsch. SDS page was employed in order to show collagen split products.Mean skin collagen content (expressed by hydroxyproline/protein) was significantly lower in patients on cyclosporin A treatment (42.4 ± 12.2µg/mg) compared to controls (78.6 ± 14.2µg/mg) and patients on corticosteroid/azathioprine therapy (73.7 ± 11.2µg/mg). Mean collagenase activity was significantly higher in patients on cyclosporin A treatment (0.59 ± 0.16 IU) compared to controls (0.21 ± 0.09 IU) and patients on corticosteroid/azathioprine treatment (0.25 ± 0.11 IU). Total skin collagen content and collagenase activity were significantly inversely correlated in patients on cyclosporin A treatment (r = -0.82,p < 0.01,y = -0.011x + 1.053). Patients on cyclosporin A treatment showed remarkable reduction of alpha 1 and alpha 2 collagen chains and significantly prominent split products.The results of our study could be explained either by the activation of collagenase or as a consequence of cyclophilin (peptidyl-prolyl cis-trans-isomerase) inhibition.