Cyclosporin A is a hormonal immunomodulator. II. Mouse study.

The present study investigated the effects of hydrocortisone (HCA) and cyclosporin A (CS) on the wet weights of various target tissues and on the plasma levels of 6 steroids and cholesterol (CH) in Swiss mice of both sexes. The effects of CS on the weights of the spleen and forestomach, as viewed from their steroid dependencies in weight change, were different for each tissue and for each sex: CS effect on the male spleen was characterized as a mixture of a major androgenic element and a minor corticosteroid-like element, whereas that on the female spleen was scored as purely androgenic. Similarly, CS effects on the male and female forestomachs were interpreted respectively as estrogenic and androgenic in nature. Both the sole use of HCA (CS-free treatment) and the combined use of HCA and CS (CS-aided treatment) increased plasma testosterone (T) and plasma CH at the expense of other plasma steroids, though minor differences were detectable between the two treatments as regards the deviation profiles of 6 steroids and cholesterol with mice of both sexes. Plasma hydrocortisone (F) in males and plasma estradiol (E2) in females were consistently resistant to the depressing effects of the 2 immunosuppressants. In conclusion, the effect of CS on the mouse immune system, as judged from the response of the spleen, was to create a state of hyperandrogenism in favor of the production of immune unresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)