Elevated chemokines and cytokines for eosinophils in neuromyelitis optica spectrum disorders

Eosinophil infiltration is one of the distinctive features in neuromyelitis optica spectrum disorders (NMOSD) but not in other demyelinating diseases including multiple sclerosis (MS). Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (eotaxin-1, -2, and -3) and monocyte chemoattractant protein (MCP)-4. We aimed to investigate the role of MCPs (MCP-1, -2, -3, and -4) and eotaxins in the acute phase of NMOSD.

Levels of serum and cerebrospinal fluid (CSF) eotaxins, MCPs, interleukin (IL)-5, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6 were measured using the cytokine multiplex assay from 26 patients with NMOSD (13 with immunotherapy, 13 without immunotherapy), 9 patients with MS, and 9 patients with other noninflammatory neurological diseases (OND). Glial fibrillary acidic protein was assessed using ELISA.

Serum MCP-1 and CSF MCP-2 levels were significantly higher in patients with NMOSD than in OND. Moreover, serum MCP-4 and CSF eotaxin-2 and -3 levels were significantly higher in NMOSD patients compared to MS and OND. Serum MCP-1, -4 and CSF eotaxin-2, -3 levels were significantly correlated with the Expanded Disability Status Scale in NMOSD. TNF-α and GM-CSF, which stimulate the above chemokines, were higher in patients with NMOSD than those in OND. Moreover, serum MCP-1 and -4 were significantly increased by IL-5 and GM-CSF stimulation, but not by TNF-α and IL-6. Only CSF eotaxin-2 was significantly increased by GM-CSF. There were no significant differences in serum MCP-1 and -4 levels between NMOSD patients with and without immunotherapy.

These findings suggest that the elevated serum MCP-1, -4 and CSF eotaxin-2, -3 may be a key step in eosinophil recruitment in the acute phase of NMOSD.