title: Inhibition of interleukin-2-mediated lymphocyte activation in patients with Cushing's syndrome: a comparison with hypocortisolemic patients.
abstract: We investigated the lymphocyte interleukin-2 (IL-2) system, which is critically involved in lymphocyte activation, in patients with disorders or the hypothalamic-pituitary-adrenal (HPA) axis. Patients with Cushing's syndrome (n = 9) showed a significant (p < 0.05) inhibition of phytohemagglutinin (PHA)-stimulated IL-2 secretion by peripheral lymphocytes and a decrease of sensitivity to cortisol inhibition in vitro compared to normal subjects (n = 9). Circulating soluble interleukin-2 receptor (sIL-2R) levels were significantly decreased (p < 0.05), whereas no significant difference was observed in PHA-induced sIL-2R release in vitro. In patients with hypocortisolism (n = 12), in vitro IL-2 synthesis was increased compared to normal subjects and to patients with Cushing's syndrome (p < 0.01). In vitro sIL-2R release was significantly higher (p < 0.01) compared to patients with Cushing's syndrome. In contrast to patients with secondary adrenal insufficiency (n = 7), patients with an adrenal origin of hypocortisolism (Addison's disease, bilateral adrenalectomy; n = 5) showed significantly elevated circulating sIL-2R levels compared to normal subjects and patients with Cushing's syndrome (p < 0.005). There was no significant difference between the study groups in mitogen-induced DNA synthesis. This is the first description of alterations of cytokine secretion in patients with HPA axis disorders. The contrary effects of long-term hypercortisolism and insufficient or absent adrenal glucocorticoid secretion on IL-2-mediated lymphocyte activation could account for the immune states previously observed in these patients.
authors.affiliation: Max-Planck-Institute of Psychiatry, Clinical Institute, München, FRG.
authors.forename: J
authors.initials: J
authors.lastname: Sauer
authors.forename: G K
authors.initials: GK
authors.lastname: Stalla
authors.forename: O A
authors.initials: OA
authors.lastname: Müller
authors.forename: E
authors.initials: E
authors.lastname: Arzt
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003480:Cushing Syndrome / Q000276:immunology*; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D007376:Interleukin-2; D004247:DNA; D006854:Hydrocortisone