Abstract
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-β/chemokine (C-C motif) ligand 4 (P<.0015), and growth factors hepatocyte growth factor (HGF) (P<.0001) and stem cell growth factor-β (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-β) 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.
Keywords
List of abbreviations:
AIS (ASIA (American Spinal Injury Association) Impairment Scale), CCL4 (chemokine (C-C motif) ligand 4), CXCL1 (chemokine (C-X-C motif) ligand 1), DPI (days postinjury), GCS (Glasgow Coma Scale), GRO (growth-related oncogene), HGF (hepatocyte growth factor), IL (interleukin), ISNCSCI (International Standards for Neurologic Classification of Spinal Cord Injury), ISS (Injury Severity Score), LOS (length of stay), MIF (macrophage migration inhibitory factor), MIP1-β (macrophage inflammatory protein 1-β), SCGF-β (stem cell growth factor-β), SCI (spinal cord injury)To read this article in full you will need to make a payment
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References
- Lifetime direct costs after spinal cord injury.Top Spinal Cord Inj Rehabil. 2011; 16: 10-16
- Epidemiology of traumatic spinal cord injury: trends and future implications.Spinal Cord. 2012; 50: 365-372
- Toll-like receptors in spinal cord injury.Curr Top Microbiol Immunol. 2009; 336: 121-136
- Neuroinflammation in spinal cord injury: therapeutic targets for neuroprotection and regeneration.Prog Brain Res. 2009; 175: 125-137
- Emerging concepts in myeloid cell biology after spinal cord injury.Neurotherapeutics. 2011; 8: 252-261
- Cerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in acute human spinal cord injury.J Neurotrauma. 2010; 27: 669-682
- Structural biomarkers in the cerebrospinal fluid within 24 h after a traumatic spinal cord injury: a descriptive analysis of 16 subjects.Spinal Cord. 2014; 52: 428-433
- Spinal cord injury: how can we improve the classification and quantification of its severity and prognosis?.J Neurotrauma. 2014; 31: 215-227
- Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF).Biochemistry. 1994; 33: 14144-14155
- The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor.J Exp Med. 1994; 179: 1895-1902
- An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction.J Exp Med. 1996; 183: 277-282
- Stabilization of atherosclerotic plaques by blockade of macrophage migration inhibitory factor after vascular injury in apolipoprotein E-deficient mice.Circulation. 2004; 109: 380-385
- MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment.Nat Med. 2007; 13: 587-596
- Macrophage migration inhibitory factor: a regulator of innate immunity.Nat Rev Immunol. 2003; 3: 791-800
- Microarray analysis of gene expression patterns in adult spinal motoneurons after different types of axonal injuries.Brain Res. 2006; 1075: 1-12
- Macrophage migration inhibitory factor induces cell death and decreases neuronal nitric oxide expression in spinal cord neurons.Neuroscience. 2006; 139: 1117-1128
- Up-regulation of macrophage migration-inhibitory factor expression after compression-induced spinal cord injury in rats.Acta Neuropathol. 2004; 108: 31-36
- Deletion of macrophage migration inhibitory factor attenuates neuronal death and promotes functional recovery after compression-induced spinal cord injury in mice.Acta Neuropathol. 2009; 117: 321-328
- 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; 94: 1498-1507
- Calculating correlation coefficients with repeated observations: Part 1–Correlation within subjects.BMJ. 1995; 310: 446
- Sepsis: current dogma and new perspectives.Immunity. 2014; 40: 463-475
- Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine.Chest. 1992; 101: 1644-1655
- Trauma patients with positive cultures have higher levels of circulating macrophage migration inhibitory factor (MIF).Res Commun Mol Pathol Pharmacol. 2000; 107: 13-20
- Imbalance between macrophage migration inhibitory factor and cortisol induces multiple organ dysfunction in patients with blunt trauma.Inflammation. 2010; 34: 193-197
- Protection from septic shock by neutralization of macrophage migration inhibitory factor.Nat Med. 2000; 6: 164-170
- Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis.Intensive Care Med. 2001; 27: 1412-1415
- Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis.Clin Infect Dis. 2007; 44: 1321-1328
- Macrophage migration inhibitory factor-A potential diagnostic tool in severe burn injuries?.Burns. 2010; 36: 335-342
- Causes of spinal cord injury.Top Spinal Cord Inj Rehabil. 2013; 19: 1-8
- Spinal cord injury and aging: challenges and recommendations for future research.Am J Phys Med Rehabil. 2012; 91: 80-93
- Methylprednisolone inhibits early inflammatory processes but not ischemic cell death after experimental spinal cord lesion in the rat.Brain Res. 1995; 672: 177-186
- Methylprednisolone and interleukin-10 reduce gray matter damage in the contused Fischer rat thoracic spinal cord but do not improve functional outcome.J Neurotrauma. 2002; 19: 653-666
- Clinical trials in spinal cord injury: lessons learned on the path to translation. The 2011 International Spinal Cord Society Sir Ludwig Guttmann Lecture.Spinal Cord. 2013; 51: 2-9
- Glucocorticoids and macrophage migration inhibitory factor (MIF) are neuroendocrine modulators of inflammation and neuropathic pain after spinal cord injury.Semin Immunol. 2014; 26: 409-414
- Differential spinal cord gene expression in rodent models of radicular and neuropathic pain.Anesthesiology. 2006; 104: 1283-1292
- Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord.Exp Neurol. 2003; 184: 313-325
- MIF as a glucocorticoid-induced modulator of cytokine production.Nature. 1995; 377: 68-71
- Exhaustion is associated with low macrophage migration inhibitory factor expression in patients with coronary artery disease.Psychosom Med. 2007; 69: 68-73
- Macrophage migration inhibitory factor is enhanced in acute coronary syndromes and is associated with the inflammatory response.PLoS One. 2012; 7: e38376
- Tetramethylpyrazine accelerates the function recovery of traumatic spinal cord in rat model by attenuating inflammation.J Neurol Sci. 2013; 324: 94-99
- Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: an in situ hybridization study.Eur J Neurosci. 1997; 9: 1422-1438
- Selective chemokine mRNA accumulation in the rat spinal cord after contusion injury.J Neurosci Res. 1998; 53: 368-376
- Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury.PLoS One. 2011; 6: e27706-e27721
- Hepatocyte growth factor reduces astrocytic scar formation and promotes axonal growth beyond glial scars after spinal cord injury.Exp Neurol. 2012; 233: 312-322
- Macrophage migration inhibitory factor exhibits a pronounced circadian rhythm relevant to its role as a glucocorticoid counter-regulator.Immunol Cell Biol. 2003; 81: 137-143
Article info
Publication history
Published online: November 15, 2014
Footnotes
Current affiliation for Chugh, New York Methodist Hospital, Brooklyn, NY.
Supported by institutional funds from The Feinstein Institute for Medical Research and The Feinstein Institute for Medical Research North Shore-Long Island Jewish Health System General Clinical Research Center (grant no. M01 RR018535) from the National Center for Research Resources, a component of the National Institutes of Health.
The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Research Resources or National Institutes of Health.
Clinical Trial Registration No.: NCT00919581.
Disclosures: none.
Identification
Copyright
© 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
