Glucocorticoid induced cytolysis of human normal and malignant lymphocytes

Contrary to the general concept that man is a "glucocorticoid resistant species" this work demonstrates distinct human lymphoid subsets which are readily lysed in vitro by upper physiological and pharmacological concentrations of cortisol. These populations include the thymocyte precursor cells, i.e. prothymocytes, and immunoactivated T lymphocytes. Chronic lymphocytic leukemia cells and malignant cells from part of the acute lymphoblastic leukemia patients were also found to be highly sensitive to the in vitro cortisol induced lysis. The leukemic cells from all acute and chronic myeloid leukemias and from some acute lymphoblastic leukemia patients were found to be completely resistant to cortisol-induced lysis, even at the super pharmacological levels of the hormone. The lysis of the sensitive cell populations was specifically induced by glucocorticoids but not by other steroid hormones. Studies of the cytolic process showed high-affinity binding of the cortisol molecule to specific cytoplasmic receptor, and implied induction of "autolytic protein" synthesis. It is suggested that the observed in vitro cortisol-induced lysis accounts for part of the clinical effects of glucocorticoids. Furthermore this phenomenon may reflect a normal regulatory mechanism exerted by the corticoadrenal hormones on the immune system.