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

Arch Phys Med Rehabil. 2013 Aug;94(8):1498-507. doi: 10.1016/j.apmr.2013.04.004. Epub 2013 Apr 22.

Abstract

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-β) (P<.016). Among subjects with SCI, the levels of SCGF-β 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.

Keywords: AIS; American Spinal Injury Association Impairment Scale; CTACK; Cytokines; GROα; HGF; IFN; IL; IL-2Ra; IQR; Inflammation; LIF; MCP-3/CCL7; MCSF; MIF; MIG/CXCL9; Macrophage migration-inhibitory factors; Rehabilitation; SCF; SCGF-β; SCI; SDF1-α; Spinal cord injuries; TNF; TRAIL; UTI; beta-nerve growth factor; cutaneous T cell–attracting chemokine; growth-related oncogene alpha; hepatocyte growth factor; interferon; interleukin; interleukin-2 receptor antagonist; interquartile range; leukemia inhibitory factor; macrophage colony-stimulating factor; macrophage migration inhibitory factor; monocyte chemoattractant protein 3/chemokine C-C motif ligand 7; monokine induced by IFN-gamma/chemokine C-X-C motif ligand 9; spinal cord injury; stem cell factor; stem cell growth factor beta; stromal-derived factor alpha; tumor necrosis factor; tumor necrosis factor-related apoptosis-inducing ligand; urinary tract infection; β-NGF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Chemokine CXCL9 / blood
  • Female
  • Hematopoietic Cell Growth Factors / blood
  • Humans
  • Interleukin-3 / blood
  • Lectins, C-Type / blood
  • Macrophage Colony-Stimulating Factor / blood
  • Macrophage Migration-Inhibitory Factors / blood*
  • Male
  • Middle Aged
  • Pilot Projects
  • Spinal Cord Injuries / blood*
  • Spinal Cord Injuries / etiology
  • Spinal Cord Injuries / pathology
  • Time Factors
  • Young Adult

Substances

  • CLEC11A protein, human
  • Chemokine CXCL9
  • Hematopoietic Cell Growth Factors
  • Interleukin-3
  • Lectins, C-Type
  • Macrophage Migration-Inhibitory Factors
  • Macrophage Colony-Stimulating Factor