Cyclosporin A: effects on the mouse thymus

Cyclosporin A (CY-A), an immunosuppressive cyclic endecapeptide, causes thymus weight reduction in mice 4 days after single oral administration. This effect was compared with that of hydrocortisone acetate (HCA), or of azathioprine (AZ). The latter had no effect on thymus weight, whereas HCA induced a marked reduction 2 days after administration. A possible mediation by the pituitary adrenal gland system (PAG) of the CY-A induced effect was suggested by the observation of an elevated corticosterone plasma level after CY-A administration and by the prevention of the thymocytolytic effect by adrenalectomy. However, the immunosuppressive activity of CY-A in humoral immunity and cell mediated tests was not affected by adrenalectomy. It must therefore be concluded that the immunosuppression produced by CY-A in vivo is not mediated by stimulation of the PAG system, contrary to its effect on the mouse thymus, which is a glucocorticosteroid effect.