Matrix metalloproteinase upregulation in chronic inflammatory demyelinating polyneuropathy and nonsystemic vasculitic neuropathy

Objective: To determine the expression pattern and cellular source of matri x metalloproteinases (MMPs) in chronic inflammatory demyelinating polyneuro pathy (CIDP) and nonsystemic vasculitic neuropathy (NSVN). Background: MMPs are endopeptidases involved in tissue destruction and infiltration by immu ne cells in multiple sclerosis and Guillain-Barre syndrome. Enzyme inhibito rs of MMPs attenuate clinical symptoms in corresponding animal models of th ese diseases. MMP inhibition may therefore be a novel approach for the trea tment of CIDP and NSVN. However, the spectrum of MMPs expressed in chronic inflammatory neuropathies has not been established. Methods: The expression of MMP-2, MMP-3, MMP-7, and MMP-9 in T cells, macrophages, and stromal cel ls in CIDP, NSVN, and noninflammatory neuropathies (NIN) was quantitated by immunohistochemistry. Results were correlated with clinical and electrophy siologic findings. Results: The production of MMP-2 and MMP-9 is increased in nerve tissue in CIDP and NSVN compared with NIN. T cells are the predomi nant source of MMP-2 and MMP-9 in CIDP and NSVN, whereas macrophages contri bute only to a minor extent. Stromal cells of the perineurium/epineurium ar e an additional source of MMP-2 in NSVN, but not in CIDP. Expression of MMP -3 and MMP-7 was not detectable in CIDP or NSVN. Expression of MMP-2 and MM P-9 did not correlate with clinical disease activity and electrophysiologic measurements. Conclusions: The upregulation of MMP-2 and MMP-9 is a specif ic feature of CIDP and NSVN, and selective inhibitors of these enzymes coul d be used to prevent inflammatory tissue damage. The similar increase of MM P-2 and MMP-9 in both demyelinating (CIDP) and nondemyelinating (NSVN) neur opathies raises doubts about whether MMPs play a primary role in demyelinat ion.