title: Serum MMPs 7-9 and their inhibitors during glucocorticoid and anti-TNF-α therapy in pediatric inflammatory bowel disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Children's Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland. laura.makitalo@helsinki.fi
authors.forename: Laura
authors.initials: L
authors.lastname: Mäkitalo
authors.forename: Hanne
authors.initials: H
authors.lastname: Rintamäki
authors.forename: Taina
authors.initials: T
authors.lastname: Tervahartiala
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.forename: Kaija-Leena
authors.initials: KL
authors.lastname: Kolho
mesh_terms: D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001799:Blood Sedimentation; D019819:Budesonide / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D005243:Feces; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D019272:Leukocyte Elastase / Q000097:blood; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D009195:Peroxidase / Q000097:blood; D011239:Prednisolone / Q000627:therapeutic use; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D039841:Leukocyte L1 Antigen Complex; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D000511:alpha-Macroglobulins; D019716:Tissue Inhibitor of Metalloproteinase-2; D019819:Budesonide; D002097:C-Reactive Protein; D011239:Prednisolone; D000069285:Infliximab; D009195:Peroxidase; D019272:Leukocyte Elastase; D020783:Matrix Metalloproteinase 7; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9