title: Identification of distinct monocyte phenotypes and correlation with circulating cytokine profiles in acute response to spinal cord injury: a pilot study.
abstract: BACKGROUND
  Macrophage infiltration to the injury site during the acute response to traumatic spinal cord injury (SCI) is not uniform. Macrophage phenotype has been characterized as either proinflammatory (M1) or anti-inflammatory (M2). Results of animal studies suggest that M1 or M2 dominance at the site of injury relates to spontaneous recovery after SCI.
  
  
  OBJECTIVE
  To investigate whether the phenotype of circulating macrophage precursors-monocytes (MO) is altered in the acute phase of SCI and corresponds to circulating inflammatory cytokines.
  
  
  METHODS
  A prospective observational cohort study.
  
  
  METHODS
  A single academic medical center in Pennsylvania.
  
  
  METHODS
  A cohort of 27 subjects with complete or incomplete traumatic SCI enrolled within 7 days after SCI injury.
  
  
  METHODS
  The MO phenotype was defined within the first week after SCI by using flow cytometry and was compared with that of historic uninjured controls. Concentrations of 25 cytokines and/or chemokines were assessed by using Luminex in serial blood samples up to 2 weeks after SCI. An analysis of variance was used to determine the correlations between the phenotypes and the cytokine profiles.
  
  
  RESULTS
  Patient subsets were identified with either M1- or M2-dominant circulating MOs distinct from the uninjured controls. The M1 dominant was associated with higher circulating levels of proinflammatory mediators interleukin (IL)12p70 and interferon gamma-induced protein 10 kDa (IP-10/CXCL10), and lower levels of anti-inflammatory cytokines IL-10, IL-15, and IL-7, whereas the M2 dominant exhibited the opposite cytokine profiles with significantly higher IL-10 and IL-7.
  
  
  CONCLUSIONS
  In the acute phase after SCI, at comparable injury severity, subgroups of patients exhibit distinct M1 or M2 MOs dominance and the phenotype is correlated with M1- or M2-specific cytokine and/or chemokine profiles. Although further studies are needed to determine how these observed phenotypic differences relate to functional recovery, our findings (1) provide the first evidence, to our knowledge, that indicates the possible individual differences in the immune responses to the comparable traumatic SCI, with potential implications for management of acute SCI and rehabilitation; and (2) may represent easily accessible biomarkers with prognostic utility.
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA; The Ferguson Laboratory for Orthopaedic Research, Department of Orthopaedic Surgery, University of Pittsburgh, PA(∗).
authors.forename: Wan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Surgery, Pittsburgh, PA; Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, Pittsburgh, PA(†).
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA(‡).
authors.forename: Mary B
authors.initials: MB
authors.lastname: Kusturiss
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA; Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA(§).
authors.forename: Derek
authors.initials: D
authors.lastname: Barclay
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA(‖).
authors.forename: Karen
authors.initials: K
authors.lastname: Greenwald
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA(¶).
authors.forename: Michael L
authors.initials: ML
authors.lastname: Boninger
authors.affiliation: Department of Health and Physical Activity, University of Pittsburgh, Pittsburgh, PA(∗∗).
authors.forename: Paul M
authors.initials: PM
authors.lastname: Coen
authors.affiliation: Department of Rehabilitation Science and Technology, University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA(††).
authors.forename: David
authors.initials: D
authors.lastname: Brienza
authors.affiliation: Department of Physical Medicine and Rehabilitation, 3471 5th Ave, Suite 201, University of Pittsburgh, Pittsburgh, PA 15213; The Ferguson Laboratory for Orthopaedic Research, Department of Orthopaedic Surgery, University of Pittsburgh, PA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA(‡‡). Electronic address: sowaga@upmc.edu.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Sowa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D010641:Phenotype; D010865:Pilot Projects; D011446:Prospective Studies; D013119:Spinal Cord Injuries / Q000097:blood*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators