Serum MMPs 7–9 and their inhibitors during glucocorticoid and anti-TNF-α therapy in pediatric inflammatory bowel disease

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OBJECTIVES: In inflammatory bowel diseases (IBD), matrix metalloproteinases (MMPs) participate in intestinal tissue damage and regenerative processes. MMP activity is inhibited by tissue inhibitors of MMPs (TIMPs) and plasma inhibitor, α₂-macroglobulin (α2M). We evaluated serum MMPs, their inhibitors and markers of neutrophil activity, myeloperoxidase (MPO) and human neutrophil elastase (HNE), during glucocorticoid (GC) and anti-TNF-α therapies in pediatric IBD, in aim to find new tools for assessment of therapeutic response. METHODS: Serum samples were collected before and within a month after the start of therapy with oral GC (n = 19) or anti-TNF-α agent (n = 16), and from 32 pediatric control patients. Serum levels of MMP-7, MMP-9, TIMP-1, TIMP-2, α2M, MPO, and HNE were analyzed with enzyme-linked immunoabsorbent assays (ELISA) and MMP-8 by immunofluorometric assay (IFMA). Disease activity was monitored with erythrocyte sedimentation rate (ESR), CRP, fecal calprotectin (FC), and physician's global assessment of clinical disease activity (PGA). RESULTS: In IBD, pretreatment serum MMP-7, MMP-8, MMP-9, α2M, MPO, and HNE were elevated compared with controls. During GC therapy, MMP-7, TIMP-1, and MMP-7/TIMP-2 decreased (all p < 0.05). During anti-TNF-α therapy, MMP-7 decreased (p = 0.063), but remained higher than that after GC therapy (p < 0.05). α2M (p < 0.05) and HNE (p < 0.05) increased, the former higher than that in GC-treated patients. The levels of MMPs and their inhibitors did not markedly associate with inflammatory markers in blood or feces. CONCLUSIONS: In pediatric IBD, serum MMP-7 mirrors disease activity, and together with TIMP-1, reflects GC therapy response. α₂-Macroglobulin expression parallels the anti-TNF-α response.