Growth inhibition by cyclosporine A in vivo and in vitro

Cyclosporine A is a commonly used immunosuppressant in organ transplant. However, in addition to its nephro- and hepato-toxicity, we now report that it also exerts growth inhibiting effects in vivo and in vitro. Rats treated with daily Cyclosporine A I.P. injections of 10 mg or 20 mg/kg body weight gained weight at significantly lower rates than controls over a six week period. This growth retardation was completely reversible. By 6 weeks post treatment, the body weights of the treated animals were the same as controls. In contrast, rats treated with lower doses of cyclosporine A (5 mg/kg) did not suffer any growth retardation throughout. In vitro, rat primary cultured fibroblasts treated with greater than 1 microgram/ml Cyclosporine A suffered 25-60% cell loss in the post-log phase but the cytotoxic effect was not apparent during the log phase of growth. Fibroblasts treated with less than or equal to 1 microgram/ml of Cyclosporine A did not suffer any cell loss. In conclusion, Cyclosporine A exerts growth inhibitory effects in vivo when given at greater than 5 mg/kg body weight and cytotoxic effects in vitro at greater than 1 microgram/ml.