We hypothesized that increased levels of blood cytokines occur in brain dead patients, and that these cytokines are responsible for some of the endocrine and/or acute-phase reactant abnormalities found in these patients. We measured blood levels of cytokines, hormones, and acute-phase reactants in 18 brain-dead potential organ donors at the moment of establishing the legal diagnosis of brain death and compared them with levels found in a control group. Although interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) levels were within the normal range, interleukin-6 (IL-6) levels were clearly above the normal range in all patients (median, 1,444 pg/mL; range, 75 to 11,780). In the brain-dead group, total thyroxine (tT(4)), free T-4 (fT(4)), triiodothyronine (T-3), thyrotropin (TSH), dehydroepiandrosterone sulfate (DHEA S), testosterone, albumin, Zn, and osteocalcin levels were decreased, T-3 resin uptake index (T-3 RUI), corticotropin (ACTH), cortisol, 11-deoxycortisol (11-DOC), 17-hydroxyprogesterone (17-OHPr), aldosterone, luteinizing hormone, and follicle-stimulating hormone levels were normal, and reverse T-3 (rT(3)), renin, and C reactive protein (CRP) levels were increased. Multiple regression analysis demonstrated significant interrelations between IL-6 and T-4, T-3, testosterone, and CRP. We also studied the evolution of some of these parameters in four patients with severe head injury who finally developed brain death. IL-6 levels on admission to the intensive care unit (ICU) were above the normal limits, as in other patients with cranial trauma, but when the patients developed brain death, there was a pronounced increase in IL-6 levels. We conclude that brain death is accompanied by high levels of IL-6. IL-6 may be partially responsible for the hormonal and acute-phase reactant abnormalities found in these patients. Copyright (C) 1995 by W.B. Saunders Company