ABSTRACT
Cyclosporin A [CyA] is utilized as an immunomodulator to stop the immunopathological reactions preceding and accompanying insulin dependent diabetes mellitus. Some published results seem promising; on the other h and, a destructive effect on the islet cells of Langerhans has been observed experimentally by some research workers. The aim of the present study was to investigate thoroughly this phenomenon to find out the eventual effect of CyA on the nondiabetic pancreas and whether this effect, if any, is dose related. For this, 40 patients receiving CyA for two years have been included in the study. 25 patients receiving a dose of 2-5 mg/kg/d, 10 patients receiving 5.1-10 mg/kg/d and 5 patients receiving more than 10 mg/kg/d. Blood glucose levels and plasma insulin levels have been measured before CyA administration and 3, 6, 12 and 24 months after it. This study has been coupled with an experimental one, using 60 male rats weighing about 100 g each divided in 4 groups receiving no drug, 5, 10 and 20 mg/kg/d, respectively, and sacrificed at the end of 1, 2, and 3 months to have the pancreas examined histologically. The effect of CyA was simulatory in the first 3 months, then the effect has been proportional to the dose the small dose having no effect, while the large dose had a suppressor one. The experimental study revealed a parallelism with the clinical results. Moreover, the number of delta cells in the islets of Langerhans has been increased with the high doses. These findings can explain the phenomena accompanying the use of CyA in the context of glucose metabolism