Chitinase effects on immune cell response in neuromyelitis optica and multiple sclerosis

Mult Scler. 2011 May;17(5):521-31. doi: 10.1177/1352458510392619. Epub 2010 Dec 15.


Background: Recent studies conducted in arthritis, asthma, and inflammatory bowel disease suggest that chitinases are important in inflammatory processes and tissue remodeling.

Objective: To investigate the role of chitinases in multiple sclerosis (MS) and neuromyelitis optica (NMO).

Methods: Levels of chitotriosidase, acid mammalian chitinase (AMCase), and chitinase 3-like-1 (CHI3L1) were measured using ELISA, in cerebrospinal fluid (CSF) and in serum from 24 patients with relapsing remitting (RR) MS, 24 patients with secondary progressive (SP) MS, 12 patients with NMO, 24 patients with other inflammatory neurological diseases (OIND), and 24 healthy controls (HCs). The number of anti-MOG cytokine-secreting cells was studied using ELISPOT. Eotaxins, MCP-1, RANTES, and IL-8 were assessed using ELISA. Cell transmigration was determined using an in vitro blood-brain barrier (BBB) model, in the presence and absence of chitinases.

Results: CSF chitinase levels were significantly increased in patients with RRMS and NMO compared with HCs and patients with SPMS and OIND. In contrast, no significant differences were detected in serum chitinase levels between groups. Chitinase CSF levels showed correlation with anti-MOG IL-13-producing cells, and eotaxin levels. In vitro experiments showed macrophage chitinase secretion was significantly increased by IL-13, but not by IL-5, IL-6, IL-12, or IFN-γ. Moreover, chitinases enhanced IL-8, RANTES, MCP-1, and eotaxin production, increasing migratory capacity in eosinophils, T cells, and macrophages across an in vitro BBB model.

Conclusions: Chitinases increased in the CSF from patients with NMO in response to IL-13. These enhanced levels could contribute to central nervous system inflammation by increasing immune cell migration across the BBB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines
  • Adult
  • Argentina
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Blood-Brain Barrier / enzymology
  • Blood-Brain Barrier / immunology
  • Case-Control Studies
  • Cells, Cultured
  • Chemokines / metabolism
  • Chitinase-3-Like Protein 1
  • Chitinases* / blood
  • Chitinases* / cerebrospinal fluid
  • Coculture Techniques
  • Cytokines / metabolism
  • Endothelial Cells / enzymology
  • Endothelial Cells / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Enzyme-Linked Immunospot Assay
  • Female
  • Glycoproteins / blood
  • Glycoproteins / cerebrospinal fluid
  • Hexosaminidases / blood
  • Hexosaminidases / cerebrospinal fluid
  • Humans
  • Lectins / blood
  • Lectins / cerebrospinal fluid
  • Leukocytes, Mononuclear / enzymology*
  • Leukocytes, Mononuclear / immunology
  • Male
  • Multiple Sclerosis, Chronic Progressive / blood
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid
  • Multiple Sclerosis, Chronic Progressive / enzymology*
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid
  • Multiple Sclerosis, Relapsing-Remitting / enzymology*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein
  • Neuromyelitis Optica / blood
  • Neuromyelitis Optica / cerebrospinal fluid
  • Neuromyelitis Optica / enzymology*
  • Neuromyelitis Optica / immunology
  • Transendothelial and Transepithelial Migration
  • Up-Regulation


  • Adipokines
  • Biomarkers
  • CHI3L1 protein, human
  • Chemokines
  • Chitinase-3-Like Protein 1
  • Cytokines
  • Glycoproteins
  • Lectins
  • MOG protein, human
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Hexosaminidases
  • chitotriosidase
  • CHIA protein, human
  • Chitinases