Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis

PLoS One. 2013 Apr 18;8(4):e61835. doi: 10.1371/journal.pone.0061835. Print 2013.


Background: Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO), relapsing remitting multiple sclerosis (RRMS), and primary progressive MS (PPMS), and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis.

Methods/principal findings: We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND) by multiplexed fluorescent bead-based immunoassay. Interleukin (IL)-17A, IL-6, CXCL8 and CXCL10 levels were significantly higher in NMO patients than in OND and RRMS patients at relapse, while granulocyte-colony stimulating factor (G-CSF) and CCL4 levels were significantly higher in NMO patients than in OND patients. In NMO patients, IL-6 and CXCL8 levels were positively correlated with disability and CSF protein concentration while IL-6, CXCL8, G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-γ were positively correlated with CSF neutrophil counts at the time of sample collection. In RRMS patients, IL-6 levels were significantly higher than in OND patients at the relapse phase while CSF cell counts were negatively correlated with the levels of CCL2. Correlation coefficients of cytokines/chemokines in the relapse phase were significantly different in three combinations, IL-6 and GM-CSF, G-CSF and GM-CSF, and GM-CSF and IFN-γ, between RRMS and NMO/NMOSD patients. In PPMS patients, CCL4 and CXCL10 levels were significantly higher than in OND patients.

Conclusions: Our findings suggest distinct cytokine/chemokine alterations in CSF exist among NMO, RRMS and PPMS. In NMO, over-expression of a cluster of Th17- and Th1-related proinflammatory cytokines/chemokines is characteristic, while in PPMS, increased CCL4 and CXCL10 levels may reflect on-going low grade T cell and macrophage/microglia inflammation in the central nervous system. In RRMS, only a mild elevation of proinflammatory cytokines/chemokines was detectable at relapse.

MeSH terms

  • Adult
  • Aquaporin 4 / immunology
  • Chemokines / cerebrospinal fluid*
  • Cytokines / cerebrospinal fluid*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / cerebrospinal fluid
  • Humans
  • Interleukin-17 / cerebrospinal fluid
  • Interleukin-6 / cerebrospinal fluid
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid*
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid*
  • Neuromyelitis Optica / cerebrospinal fluid*
  • Recurrence


  • AQP4 protein, human
  • Aquaporin 4
  • Chemokines
  • Cytokines
  • Interleukin-17
  • Interleukin-6
  • Granulocyte-Macrophage Colony-Stimulating Factor

Grants and funding

This study was supported by a Health and Labour Sciences Research Grant on Intractable Diseases (H22-Nanchi-Ippan-130 and H23-Nanchi-Ippan-017) from the Ministry of Health, Labour, and Welfare, Japan (, by a Scientific Research B Grant (No. 22390178) and a Challenging Exploratory Research Grant (No. 23659459) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.