title: Natural killer cell activity in the peripheral blood of patients with Cushing's syndrome.
abstract: BACKGROUND
  Natural killer (NK) cells are CD3(-)CD16(+)CD56(+) bone-marrow-derived lymphocytes mediating first-line defence by direct cytotoxicity against various types of target cells without prior immunization. NK cell activity is positively regulated by immune interferon (IFN-gamma); among hormones, glucocorticoids are potent in vitro and in vivo inhibitors, whereas ACTH and beta-endorphin in many experimental circumstances enhance NK cytotoxicity.
  
  
  METHODS
  We measured NK cytotoxicity of peripheral blood mononuclear cells (PBMC) obtained at 0800h and 2000h from 26 patients with Cushing's syndrome (12 pituitary-dependent, 12 adrenal-dependent and two dependent on ectopic ACTH secretion). In vitro responsiveness to IFN-gamma or cortisol was also tested.
  
  
  METHODS
  NK activity was measured in a 4-h direct cytotoxicity assay using K562 cells as targets. Plasma ACTH, serum and urinary free cortisol were concomitantly measured with commercially available kits.
  
  
  RESULTS
  Spontaneous activity and responsiveness to IFN-gamma or cortisol were significantly greater in 15 age- and sex-matched controls than in Cushing's patients at 0800h. In pituitary-dependent Cushing's patients, plasma ACTH correlated positively with mean levels of spontaneous NK activity (r=0.64, P<0.05) and negatively with cortisol-dependent percentage inhibition (r=-0.69, P<0.02). In adrenal-dependent Cushing's patients, a negative correlation was observed between levels of spontaneous NK activity and urinary free cortisol (r=-0.67, P<0.02).
  
  
  CONCLUSIONS
  Our data indicate that excess endogenous glucocorticoids affect spontaneous NK cell activity and responsiveness to exogenous IFN-gamma or cortisol. The differential patterns observed between pituitary-dependent and adrenal-dependent groups are compatible with a positive immunomodulatory role of pituitary pro-opiomelanocortin-derived peptides that effectively counterbalance, at least partially, glucocorticoid immunosuppression.
authors: Clinica Medica Generale, Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino, Regione Gonzole 10, 10043 Orbassano (Torino), Italy.
authors: R G
authors: RG
authors: Masera
authors: A
authors: A
authors: Staurenghi
authors: M L
authors: ML
authors: Sartori
authors: A
authors: A
authors: Angeli
mesh_terms: D000302:Adrenal Cortex / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology / Q000652:urine; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D010902:Pituitary Gland / Q000503:physiopathology; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D007371:Interferon-gamma; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone