Macrophage migration inhibitory factor is a critical mediator of systemic inflammatory response syndrome

Objective: To determine the relations between macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and cortisol in patients with systemic inflammatory response syndrome (SIRS) and to determine whether their levels correlate with patient survival. Design: Prospective, observational, cohort study. Setting: General intensive care unit in a university hospital. Patients and participants: The study included 17 consecutive patients who met the criteria for SIRS; the patients were classified into subgroups, survivors (n = 8) and nonsurvivors (n = 9); eight healthy volunteers served as control subjects. Interventions: None. Measurements and results: Serum MIF, TNF-alpha, IFN-gamma, and cortisol levels were measured serially when the patients were first identified as having SIRS (day 0), and on days 1-4. Except for the high tendency of acute respiratory distress syndrome in nonsurvivors (44%) compared to survivors (13%), there were no differences in the clinical backgrounds of the patients between the two groups. All patients had multiple organ dysfunction syndrome. The values of MIF and TNF-alpha in the nonsurvivors were significantly more elevated than those cytokines measured in the survivors and control subjects. Peak MIF levels significantly correlated with peak TNF-alpha levels (r(2) = 0.448, P = 0.002), but did not correlate with peak levels of cortisol and IFN-gamma. Although the levels of IFN-gamma and cortisol showed a marked increase compared to those of the control subjects, we could not find differences in these variables between the survivors and the nonsurvivors. Conclusions: High MIF and TNF-alpha levels are closely linked with poor outcome in patients with SIRS. MIF and TNF-alpha may act together and have pathogenic roles in SIRS.