Lymphoid cells produce an immunoregulatory glucocorticoid increasing factor (GIF) acting through the pituitary gland.

Products are released in vitro by mitogen stimulation of human peripheral blood mononuclear cells or rat spleen cells which increase corticosterone blood levels when injected into normal rats. We report that an almost pure population of human peripheral blood lymphocytes in mixed lymphocyte culture stimulated with phytohaemagglutinin also produces a glucocorticoid increasing factor(s). The product equivalent to the amount released by 5 X 10(5) cells increased corticosterone levels four-fold and also increased ACTH levels. When rats were hypophysectomized or treated with dexamethasone to block ACTH output, no corticosterone increase was noted following administration of glucocorticoid increasing factor(s) (GIF). Similar results were obtained with supernatants of rat spleen cells stimulated with concanavalin A. We conclude that GIF has no direct action on the adrenals in vivo and that a functional pituitary gland is essential for its action. The presented data taken together with those described earlier suggest the existence of a glucocorticoid associated immunoregulatory feedback circuit.