Differential potencies of corticosterone and hydrocortisone in immune and immune-related processes in the mouse.

The effects of corticosterone and hydrocortisone on the thymus, the pituitary--adrenal axis, delayed hypersensitivity, the corticosterone plasma level and the numbers of circulating nucleated and monocytic cells were investigated in the mouse. Short-term effects within 48 h after one or two corticoid injections and late effects 7 days after a regimen of 4 corticoid injections were discerned. In short-term experiments hydrocortisone was more active than corticosterone upon the induction of leukopenia and monocytopenia and the inhibition of delayed hypersensitivity. However, regarding late effects and the short-term effect on adrenal weight, corticosterone far exceeded hydrocortisone in activity. Our results could be explained by assuming two feedback-inhibition systems for glycocorticoids. The first, likely to be responsible for the changes observed for the adrenal weight and the numbers of ciruclating white cells after a single glucocorticoid injection, was shown to be expressed in a soluble factor released in the blood stream tentatively designated "glucocorticoid inhibiting factor. The factor was more readily induced by hydrocortisone but displayed a greater specificity in inhibiting effects of corticosterone. The second feedback-inhibition system, responsible for increased numbers of circulating monocytes paralleled by an enhanced delayed hypersensitivity response, was expressed in a decreased corticosterone plasma level, most probably secondary to a diminished release of ACTH from the pituitary gland. With the glucocorticoid doses we used the second feedback-inhibition system was only triggered by the more physiological hormone, corticosterone.