Macrophage migration inhibitory factor and hypothalamo-pituitary-adrenal function during critical illness

In patients with septic shock (n = 32), multitrauma (n = 8), and hospitaliz ed matched controls (n = 41), we serially measured serum macrophage inhibit ory factor (MIF), cortisol, plasma ACTH, tumor necrosis factor-alpha, and i nterleukin-6 (IL-6) immunoreactivity during 14 days or until discharge/deat h. MIF levels were significantly elevated on day 1 in septic shock (14.3 +/ - 4.5 mug/L), as opposed to trauma (3.1 +/- 1.7 mug/L) and control patients (2.5 +/- 2.1 mug/L). The time course of MIF, parallel to cortisol, but in contrast to ACTH, showed persistently elevated levels in septic patients. O n admission, nonsurvivors of septic shock (n = 11) showed significantly hig her MIF levels than survivors (18.4 +/- 4.8 and 10.2 +/- 4.2 mug/L, respect ively). Patients with septic adult respiratory distress syndrome (ARDS; n = 8) showed higher MIF levels than those who did not develop ARDS (19.4 +/- 4.7 vs. 9.2 +/- 4.3 mug/L, respectively). Multiple logistic regression anal ysis demonstrated that both MIF and ARDS were independent predictors of adv erse outcome. On admission, tumor necrosis factor-alpha, IL-6, procalcitoni n, and lipopolysaccharide-binding protein levels were higher in patients wi th septic shock than in patients with multitrauma. In septic patients, regr ession analysis showed significant correlations between MIF and cortisol as well as between MIF and IL-6 levels and disease severity scores. No relati on was found between MIF and markers of the acute phase response (procalcit onin, C-reactive protein, and lipopolysaccharide-binding protein). In multi trauma patients, MIF levels were not elevated at any time point and were no t related to other variables. Our data suggest that during immune-mediated inflammation (such as septic s hock) MIF is an important neuroendocrine mediator: a contraregulator of the immunosuppressive effects of glucocorticoids.