Human immunoglobulin G suppresses the production of matrix metalloproteinase‐9 in peripheral blood mononuclear cells of patients with multiple sclerosis

Abstract

Objective Matrix metalloproteinase (MMP)-9 is a key molecule that indicates disruption of the blood-brain barrier (BBB), and is recognized as a candidate biomarker of disease activity in multiple sclerosis (MS). The aim of the present study was to determine whether human immunoglobulin G (hIgG) could reduce the production of MMP-9 in peripheral blood mononuclear cells (PBMC) from patients with MS. Methods We investigated the effect of hIgG on the expression of MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in PBMC of patients with relapsing-remitting MS (RRMS) compared with healthy controls (HC) in vitro. Results Patients with RRMS were not receiving any disease-modifying therapies when blood was sampled in this study. Although levels of MMP-9 and TIMP-1 in PBMC were not different between RRMS and HC groups, the MMP-9/TIMP-1 ratio was significantly increased in patients with RRMS when compared with HC. PBMC that were stimulated with lipopolysaccharide (LPS, 1 lg/mL) expressed a higher level of MMP-9 in RRMS than the HC groups, although the level of TIMP-1 was equal between groups. hIgG reduced the level of MMP-9 in PBMC from both patients with RRMS and HC with LPS stimulation in a dose-dependent manner, but had no effect on the expression of TIMP-1. The MMP-9/TIMP-1 ratio in both patients with RRMS and HC was also decreased by hIgG. The effect of hIgG was not through neutralization of MMP-9. hIgG alone did not induce MMP-9 mRNA, and suppressed the upregulation of mRNA in PBMC stimulated with LPS. Conclusions These results suggest that hIgG could be effective in treating patients with RRMS though the inhibition of the transmigration of immune cells into the brain parenchyma.

Intravenous immunoglobulin and suppression of the production of matrix metalloproteinase‐9

“…Okada and Adachi reported the MMP‐9/TIMP‐1 ratio of peripheral blood mononuclear cell (PBMC) from MS patients increased when stimulated with lipopolysaccharide (LPS), even during the remission period, suggesting impaired MMP‐9/TIMP‐1 balance predisposed MS relapse. PBMC of such MS patients could induce blood–brain barrier destruction through the MMP‐9 activation at non‐specific inflammation, independent of central nervous system antigen stimulation, which could facilitate migration of activated T cells and macrophages from the circulation into the central nervous system.…”