Within the chemokine family, particularly studied members in the course of MS are the monocyte chemotactic proteins (MCPs), with MCP-1 and MCP-2 being selectively expressed at high levels in active lesions, while MCP-3 was mostly observed in the extracellular matrix surrounding the vascular elements .
Nonetheless, several animal and in vitro evidence connected both MMPs to IL-18  and to the IL-17/IL-23 axis , demonstrating a general stimulating effect on the enzymes production, whereas other reports suggested a regulation of MMP-2 on MCP-3 activity  showing an anti-inflammatory effect .
IL-17A, IL23, and MCP-3 levels were simultaneously measured in sera and CSF of patients, twofold diluted with dilution buffer or undiluted, respectively, by a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) system based on chemiluminescence detection (Aushon SearchLight chemiluminescent assay kits, Tema Ricerca, Italy) according to the manufacturer's recommendations.
The levels of IL-17, IL-18, IL-23, and MCP-3 in the serum of OND and MS patients were detectable in 21% of samples for IL-17 (16 OND and 22 MS), 86% for IL-18 (79 OND and 77 MS), 71% for IL-23 (65 OND and 64 MS), and 61% for MCP-3 (55 OND and 55 MS).
As reported in Table 2, we observed significant positive correlations between MCP-3 and IL-17, between MCP-3 and IL-23, and between IL-17 and IL-23.
Notably, we found a positive correlation between IL-18 and active MMP-2 and MCP-3 and IL-17 and between IL-18 and IL-23.
In addition, the cytokine abnormal values were merged in one category (Table 4, combined interleukins), including subjects with at least one abnormal value of IL-17, IL-18, IL-23, or MCP-3.
In light of the above considerations, we set out the present study with the aim to evaluate the contribution of MMPs, namely, active MMP-9 and MMP-2, and the cytokines/chemokines IL-17, IL-18, IL-23, and MCP-3 to the pathogenesis of MS.
Of note, to the best of our knowledge, there are no data in literature about MCP-3 circulating levels.
The observed strong correlations between IL-17, IL-23, and MCP-3 in the serum and between MCP-3, IL-17, IL-18, and IL-23 in the CSF of MS patients suggest that, though not massive, the MS pathology might be characterized by a general overproduction of cytokines and chemokines.
Brosnan, "MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: an immunohistochemical and in situ hybridization study," Journal of Neuroimmunology, vol.