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Use of MMP-8 and MMP-9 to assess disease severity in children with viral lower respiratory tract infections.

Abstract

Matrix metalloproteinases (MMPs) play an important role in respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease. It was hypothesized that MMP-8 and MMP-9 may function as biological markers to assess disease severity in viral lower respiratory tract infections in children. MMP-8 and MMP-9 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) and granulocytes obtained in both the acute and recovery phase from 153 children with mild, moderate, and severe viral lower respiratory tract infections were determined using real-time PCR. In addition, MMP-8 and MMP-9 concentrations in blood and nasopharyngeal specimens were determined during acute mild, moderate, and severe infection, and after recovery using ELISA. Furthermore, PBMCs and neutrophils obtained from healthy volunteers were stimulated with RSV, LPS (TLR4 agonist), and Pam3Cys (TLR2 agonist) in vitro. Disease severity of viral lower respiratory tract infections in children is associated with increased expression levels of the MMP-8 and MMP-9 genes in both PBMCs and granulocytes. On the contrary, in vitro experiments showed that MMP-8 and MMP-9 mRNA and protein expression in PBMCs and granulocytes is not induced by stimulation with RSV, the most frequent detected virus in young children with viral lower respiratory tract infections. These data indicate that expression levels of the MMP-8 and MMP-9 genes in both PBMCs and neutrophils are associated with viral lower respiratory tract infections disease severity. These observations justify future validation in independent prospective study cohorts of the usefulness of MMP-8 and MMP-9 as potential markers for disease severity in viral respiratory infections.

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  • Publisher Full Text
  • Authors

    Brand KH, Ahout IM, de Groot R, Warris A, Ferwerda G, Hermans PW

    Institution

    Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

    Source

    Journal of medical virology 84:9 2012 Sep pg 1471-80

    MeSH

    Female
    Gene Expression
    Granulocytes
    HeLa Cells
    Humans
    Infant
    Leukocytes, Mononuclear
    Male
    Matrix Metalloproteinase 8
    Matrix Metalloproteinase 9
    Nasal Mucosa
    Neutrophils
    Pharynx
    Prospective Studies
    Respiratory Syncytial Virus Infections
    Respiratory Syncytial Viruses
    Respiratory Tract Infections
    Severity of Illness Index
    Statistics, Nonparametric

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22825827