We monitored serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) before and during intravenously applied immunoglobulin (IVIG) therapy in 33 patients with chronic immune-mediated neuropathies and myopathies and 15 controls. Baseline MMP-2 and TIMP-2 serum levels were lower and MMP-9 and TIMP-1 serum levels higher in all patients compared to age-matched controls. Eight days after IVIG treatment, MMP-2, TIMP-2, and TIMP-1 serum levels increased, while MMP-9 serum levels decreased, indicating tissue repair. After 60 days, MMP-9 levels increased, MMP-2 approached normal levels, while TIMP-1 and TIMP-2 serum levels were below day 8 levels, indicating relapsing tissue damage. Comparing the MMP/TIMP results with the clinical courses, IVIG treatment tended to change MMP/TIMP levels in a way that paralleled clinical improvement and relapse. In sum, during a distinct time period, IVIG therapy seems to be able to modulate MMP-mediated tissue repair.

1.
Baker AH, Edwards DR, Murphy G: Metalloproteinase inhibitors: biological action and therapeutic opportunities. J Cell Sci 2002;115:3719–3727.
2.
Carmeli E, Moas M, Reznick AZ, Coleman R: Matrix metalloproteinases and skeletal muscle: a brief review. Muscle Nerve 2004;29:191–197.
3.
Kugler A: Matrix metalloproteinases and their inhibitors. Anticancer Res 1999;19:1589–1592.
4.
Choi YC, Dalakas MC: Expression of matrix metalloproteinases in the muscle of patients with inflammatory myopathies. Neurology 2000;54:65–71.
5.
Hartung HP, Kieseier BC: The role of matrix metalloproteinases in autoimmune damage to the central and peripheral nervous system. J Neuroimmunol 2000;107:140–147.
6.
Kieseier BC, Schneider C, Clements JM, Gearing AJ, Gold R, Toyka KV, Hartung HP: Expression of specific matrix metalloproteinases in inflammatory myopathies. Brain 2001;124:341–351.
7.
Schoser BGH, Blottner D, Stuerenburg HJ: Matrix metalloproteinases in inflammatory myopathies: enhanced immunoreactivity near atrophic myofibers. Acta Neurol Scand 2002;105:309–313.
8.
Demestre M, Wells GM, Miller KM, Smith KJ, Hughes RAC, Gearing AJ, Gregson NA: Characterisation of matrix metalloproteinases and the effects of a broad-spectrum inhibitor (BB-1101) in peripheral nerve regeneration. Neuroscience 2004;124:767–779.
9.
Dalakas MC: The use of intravenous immunoglobulin in the treatment of autoimmune neuromuscular diseases: evidence-based indications and safety profile. Pharmacol Ther 2004;102:177–193.
10.
Wiles CM, Brown P, Chapel H, et al: Intravenous immunoglobulin in neurological disease: a specialist review. J Neurol Neurosug Psychiatry 2002;72:440–448.
11.
Lee MA, Palace J, Stabler G, Ford J, Gearing A, Miller K: Serum gelatinases B, TIMP-1 and TIMP-2 levels in multiple sclerosis. Brain 1999;122:191–197.
12.
Mirowska D, Wicha W, Czlonkowski A, Czlonkowska A, Weber F: Increase of matrix metalloproteinase-9 in peripheral blood of multiple sclerosis patients treated with high doses of methylprednisolone. J Neuroimmunol 2004;146:171–175.
13.
Sharshar T, Durand MC, Lefaucheur JP, Lofaso F, Raphael JC, Gherardi RK, Creange A: MMP-9 correlates with electrophysiological abnormalities in Guillain-Barré syndrome. Neurology 2002;59:1649–1651.
14.
Shapiro S, Shoenfeld Y, Gilburd B, Sobel E, Lahat N: Intravenous γ-globulin inhibits the production of matrix metalloproteinase-9 in macrophages. Cancer 2002;95:2032–2037.
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