Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis

Eur J Neurol. 2009 Jun;16(6):771-4. doi: 10.1111/j.1468-1331.2009.02560.x. Epub 2009 Feb 19.

Abstract

Background and purpose: Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS.

Methods: We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1beta (MIP-1beta), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients.

Results: MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum (P < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis (r = -0.407; P = 0.075).

Conclusions: We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease.

MeSH terms

  • Amyotrophic Lateral Sclerosis / blood
  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid
  • Amyotrophic Lateral Sclerosis / diagnosis*
  • Biomarkers / analysis
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Chemokine CCL2 / analysis
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / cerebrospinal fluid
  • Chemokines / analysis*
  • Chemokines / blood
  • Chemokines / cerebrospinal fluid
  • Disease Progression
  • Early Diagnosis
  • Gliosis / blood
  • Gliosis / cerebrospinal fluid
  • Gliosis / diagnosis
  • Humans
  • Inflammation / blood
  • Inflammation / cerebrospinal fluid
  • Inflammation / diagnosis*
  • Interleukin-8 / analysis
  • Interleukin-8 / blood
  • Interleukin-8 / cerebrospinal fluid
  • Microglia / immunology
  • Microglia / metabolism
  • Predictive Value of Tests
  • Prognosis
  • Sensitivity and Specificity
  • Time Factors
  • Up-Regulation / immunology

Substances

  • Biomarkers
  • CCL2 protein, human
  • Chemokine CCL2
  • Chemokines
  • Interleukin-8