Elevated circulating levels of the pro-inflammatory cytokine macrophage migration inhibitory factor in individuals with acute spinal cord injury.

OBJECTIVE: To test the hypothesis that macrophage migration inhibitory factor (MIF) is elevated in the circulation of individuals with acute spinal cord injury (SCI) compared with uninjured individuals. DESIGN: Prospective, observational pilot study. SETTING: Academic medical center. PARTICIPANTS: Adults with acute traumatic SCI (n=18) and uninjured participants (n=18), comparable in age and sex distribution. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary outcome measure was the plasma MIF levels. Potential correlations were examined between MIF and clinical/demographic variables. The secondary outcome was to determine if other immune mediators were elevated in participants with acute SCI and if their levels correlated with the MIF. RESULTS: MIF was significantly elevated in subjects with acute SCI compared with control subjects at 0 to 3 (P<.0029), 4 to 7 (P<.0001), and 8 to 11 (P<.0015) days postinjury (DPI). At 0 to 3 DPI, levels of cytokines interleukin-6 (P<.00017), interleukin-9 (P<.0047), interleukin-16 (P<.007), interleukin-18 (P<.014), chemokines growth-related oncogene α/chemokine (C-X-C motif) ligand 1 (P<.0127) and macrophage inflammatory protein 1-ß/chemokine (C-C motif) ligand 4 (P<.0015), and growth factors hepatocyte growth factor (HGF) (P<.0001) and stem cell growth factor-ß (P<.0103) were also significantly elevated in subjects with acute SCI. With the exception of interleukin-9, all of these factors remained significantly elevated at 4 to 7 DPI; a subset (interleukin-16, HGF, stem cell growth factor-ß) remained elevated throughout the study. Within individuals, MIF levels correlated with HGF (P<.018) and interleukin-16 (P<.01). CONCLUSIONS: These data demonstrate that MIF is significantly elevated in subjects with acute SCI, supporting further investigation of MIF and other inflammatory mediators in acute SCI, where they may contribute to primary and secondary functional outcomes.

Pilot study: elevated circulating levels of the proinflammatory cytokine macrophage migration inhibitory factor in patients with chronic spinal cord injury.

OBJECTIVE: To test the hypothesis that the proinflammatory cytokine macrophage migration inhibitory factor (MIF) is elevated in the circulation of patients with chronic spinal cord injury (SCI) relative to uninjured subjects, and secondarily to identify additional immune mediators that are elevated in subjects with chronic SCI. DESIGN: Prospective, observational pilot study. SETTING: Outpatient clinic of a department of physical medicine and rehabilitation and research institute in an academic medical center. PARTICIPANTS: Individuals with chronic (>1y from initial injury) SCI (n=22) and age- and sex-matched uninjured subjects (n=19). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Plasma levels of MIF, as determined by a commercially available multiplex suspension immunoassay. The relationship between MIF levels and clinical/demographic variables was also examined. As a secondary outcome, we evaluated other cytokines, chemokines, and growth factors. RESULTS: Plasma MIF levels were significantly higher in subjects with chronic SCI than in control subjects (P<.001). Elevated MIF levels were not correlated significantly with any one clinical or demographic characteristic. Subjects with SCI also exhibited significantly higher plasma levels of monokine induced by interferon-gamma/chemokine C-X-C motif ligand 9 (P<.03), macrophage colony stimulating factor (P<.035), interleukin-3 (P<.044), and stem cell growth factor beta (SCGF-ß) (P<.016). Among subjects with SCI, the levels of SCGF-ß increased with the time from initial injury. CONCLUSIONS: These data confirm the hypothesis that MIF is elevated in subjects with chronic SCI and identify additional novel immune mediators that are also elevated in these subjects. This study suggests the importance of examining the potential functional roles of MIF and other immune factors in subjects with chronic SCI.