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PLoS By Category | Recent PLoS Articles
Immunology - Neurological Disorders - Pediatrics and Child Health

Elevated Cerebral Spinal Fluid Cytokine Levels in Boys with Cerebral Adrenoleukodystrophy Correlates with MRI Severity
Published: Thursday, February 16, 2012
Author: Troy C. Lund et al.

by Troy C. Lund, Paul S. Stadem, Angela Panoskaltsis-Mortari, Gerald Raymond, Weston P. Miller, Jakub Tolar, Paul J. Orchard

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.

Methodology/Principal Findings

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/Significance

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.

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