title: Elevated cerebral spinal fluid cytokine levels in boys with cerebral adrenoleukodystrophy correlates with MRI severity.
abstract: BACKGROUND
  X-linked adrenoleukodystrophy (ALD) is a metabolic, peroxisomal disease that results from a mutation in the ABCD1 gene. The most severe course of ALD progression is the cerebral inflammatory and demyelinating form of the disease, cALD. To date there is very little information on the cytokine mediators in the cerebral spinal fluid (CSF) of these boys.
  
  
  RESULTS
  Measurement of 23 different cytokines was performed on CSF and serum of boys with cerebral ALD and patients without ALD. Significant elevations in CSF IL-8 (29.3±2.2 vs 12.8±1.1 pg/ml, p = 0.0001), IL-1ra (166±30 vs 8.6±6.5 pg/ml, p = 0.005), MCP-1 (610±47 vs 328±34 pg/ml, p = 0.002), and MIP-1b (14.2±1.3 vs 2.0±1.4 pg/ml, p<0.0001) were found in boys with cALD versus the control group. The only serum cytokine showing an elevation in the ALD group was SDF-1 (2124±155 vs 1175±125 pg/ml, p = 0.0001). The CSF cytokines of IL-8 and MCP-1b correlated with the Loes MRI severity score (p = 0.04 and p = 0.008 respectively), as well as the serum SDF-1 level (p = 0.002). Finally, CSF total protein was also significantly elevated in boys with cALD and correlated with both IL-8, MCP-1b (p = 0.0001 for both), as well as Loes MRI severity score (p = 0.0007).
  
  
  CONCLUSIONS
  IL-8, IL-1ra, MCP-1, MIP-1b and CSF total protein were significantly elevated in patients with cALD; IL-8, MCP-1b, and CSF total protein levels correlated with disease severity determined by MRI. This is the largest report of CSF cytokine levels in cALD to date, and identification of these key cytokines will provide further insight into disease progression and perhaps lead to improved targeted therapies.
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota, United States of America. lundx072@umn.edu
authors.forename: Troy C
authors.initials: TC
authors.lastname: Lund
authors.forename: Paul S
authors.initials: PS
authors.lastname: Stadem
authors.forename: Angela
authors.initials: A
authors.lastname: Panoskaltsis-Mortari
authors.forename: Gerald
authors.initials: G
authors.lastname: Raymond
authors.forename: Weston P
authors.initials: WP
authors.lastname: Miller
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
mesh_terms: D000326:Adrenoleukodystrophy / Q000175:diagnosis*; D054407:Chemokine CCL4; D002648:Child; D016207:Cytokines / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8; D008279:Magnetic Resonance Imaging; D008297:Male; D012720:Severity of Illness Index
chemical_list: D054407:Chemokine CCL4; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8