Macrophage migration inhibitory factor in cerebrospinal fluid from patients with central nervous system infection

INTRODUCTION: Macrophage migration inhibitory factor (MIF) plays an essential pathophysiological role in septic shock, but its role in central nervous system infection (CNS) remains to be defined. METHODS: We investigated cerebrospinal fluid (CSF) levels of MIF in 171 patients who were clinically suspected of having meningitis on admission. Of these, 31 were found to have purulent meningitis of known aetiology, 20 purulent meningitis of unknown aetiology, 59 lymphocytic meningitis and 11 encephalitis, whereas 50 were suspected of having but had no evidence of CNS infection. RESULTS: CSF MIF levels were significantly higher in patients with purulent meningitis of known aetiology (median [interquartile range]: 8,639 [3,344 to 20,600] ng/l) than in patients with purulent meningitis of unknown aetiology (2,209 [1,516 to 6,550] ng/l; Mann-Whitney test, P = 0.003), patients with lymphocytic meningitis (1,912 [1,302 to 4,105] ng/l; P < 0.001) and patients suspected of having but without evidence of CNS infection (1,472 [672 to 3,447] ng/l; P < 0.001). Also, patients with encephalitis (6,937 [3,961 to 8,353] ng/l) had higher CSF MIF than did patients without CNS infection (P < 0.01). Among patients with purulent meningitis, CSF MIF levels were significantly higher in patients infected with pneumococci than in those with meningococcal infection (11,569 [8,615 to 21,935] ng/l versus 5,006 [1,717 to 10,905] ng/l; P = 0.02), in patients who required versus those not requiring assisted ventilation (10,493 [5,961 to 22,725] ng/l versus 3,240 [1,563 to 9,302] ng/l; P = 0.003), and in patients with versus those without impaired consciousness (8,614 [3,344 to 20,935] ng/l versus 2,625 [1,561 to 7,530] ng/l; P = 0.02). CSF MIF levels correlated significantly with meningeal inflammation (P < 0.05) but not with systemic inflammatory response (P > 0.05) in patients with purulent meningitis of known aetiology, those with lymphocytic meningitis and those with encephalitis. CONCLUSIONS: MIF was significantly increased in the CSF of patients with purulent meningitis and encephalitis, and was to some degree associated with severity of the infection. Our findings indicate that MIF may play an important role in CNS infection.