Macrophage migration inhibitory factor as a counter‐regulatory mediator of cortisol during septic shock

Background Migration inhibitory factor (MIF) is a widely expressed protein that is secreted in response to inflammatory or hormonal stimuli. MIF is both an endocrine hormone and immunological mediator that counter‐regulates glucocorticoid (GC) action. The anti‐inflammatory and immunosuppressive properties of GC are often beneficial but host homeostasis requires counter‐regulatory systems for which MIF has been proposed. Methods Using a time‐resolved fluorometric immunoasssay to detect serum MIF levels in patients with septic shock or multitrauma, the relation of MIF to cortisol and adrenocorticotrophic hormone (ACTH) was studied. Serum MIF, cortisol and ACTH were measured serially over 14 days in patients with septic shock ( n = 28) and multitrauma ( n = 5), and in healthy controls ( n = 41). Haemodynamics, Acute Physiology and Chronic Health Evaluation II scores and intensive care unit deaths were also recorded. Results MIF levels were raised significantly on day 1 in septic shock (mean(s.d.) 12·5(3·7) ng ml −1 ) compared with trauma (3·1(1·7) ng ml −1 ) and controls (2·5(2·1) ng ml −1 ). The time course of both MIF and cortisol showed persistently high levels in sepsis, independent of shock reversal or haemodynamics. Non‐survivors had higher MIF levels than survivors from septic shock ( P < 0·05). Regression analysis showed a significant correlation between MIF and cortisol levels ( r = 0·72), but no correlation was found between MIF and other variables. Conclusion Increased serum MIF levels occurred in septic shock compared with trauma and controls. In septic shock a clear correlation was found between MIF and cortisol levels, suggesting a parallel increase of MIF with cortisol and indicating a counter‐regulatory activity of MIF to dampen the protective effects of GC. Non‐survivors had higher MIF levels at most time points, indicating that MIF might be a potential prognostic marker in septic shock. © 2000 British Journal of Surgery Society Ltd