Effects of cyclosporine on adrenocortical stress response of Wistar rats

The effects of cyclosporine on the adrenocortical stress response in Wistar male rats were examined. The adrenocortical response to cold exposure as assessed by serum corticosterone levels was suppressed significantly (25.2%) following the oral administration of 10 mg/kg/day cyclosporine for 10 days compared to that of controls (p less than 0.05). Stress response to cold exposure was also suppressed significantly to a greater extent in rats coadministered with cyclosporine plus 1 or 4 mg/kg/day of prednisolone than in rats administered with each dose of prednisolone alone (16.8% greater for 1 mg/kg prednisolone group; p less than 0.01, or 22.3% greater for 1 mg/kg prednisolone group; p less than 0.005). Stress response of ACTH was also suppressed significantly to a greater extent in animals coadministered with cyclosporine plus 1 or 4 mg/kg/day of prednisolone than in rats administered with each dose of prednisolone alone (37.5% greater for 1 mg/kg prednisolone group; p less than 0.025, or 25.7% greater for 4 mg/kg prednisolone group; p less than 0.025). However, the decrement in ACTH levels by cyclosporine did not always result in corresponding decrement of serum corticosterone levels. These results suggest that cyclosporine decreases the adrenocortical response in part via suppression of the pituitary-adrenal axis. However, direct effects of cyclosporine on the adrenal gland should not be neglected.