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-g. 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.
Discussion: The authors suggest that CHIL31 could be used as a prognostic biomarker of conversion to MS. During the presentation, the audience chipped in with some inputs that Eotaxins have been shown to inhibit adult neurogenesis and that microglia have been broadly classified as M1 and M2 the former being neuroinflammatory and the latter playing a neuroprotective role. Chitotriosidase has been shown to play a protective role in malaria.
The paper was ardently discussed as the recent research in our lab intriguingly falls on the same line of findings. So far the researches indicate towards a potential role of such chitinases in mediating inflammation in neuroinflammatory disorders. Our research however shows tremendous increase of CSF chitinases' levels in the neurodegeneration associated with the motor neuron disease as well. Also, the upregulation of these proteins in the innate immune cells of the CNS in our disease models was also much discussed. The discussion ended with certain questions unanswered; like the impact of this upregulation on the pathogenesis/ progression of the disease, and potential of these proteins as effective biomarker, and possibly, therapeutic targets in the disease.