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Dermatitis as a component of the fetal inflammatory response syndrome is associated with activation of Toll-like receptors in epidermal keratinocytes

Authors

  • Y M Kim,

    1. Perinatology Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD and Detroit, MI
    2. Department of Pathology
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  • R Romero,

    1. Perinatology Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD and Detroit, MI
    2. Center for Molecular Medicine and Genetics
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  • T Chaiworapongsa,

    1. Perinatology Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD and Detroit, MI
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
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  • J Espinoza,

    1. Perinatology Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD and Detroit, MI
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
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  • G Mor,

    1. Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT, USA
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  • C J Kim

    1. Perinatology Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD and Detroit, MI
    2. Department of Pathology
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  • Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

Roberto Romero MD or Chong Jai Kim MD, PhD, Perinatology Research Branch, NICHD/NIH/DHHS, Hutzel Women's Hospital, 3990 John R 4 Brush, Detroit, MI 48201, USA. e-mail: warfiela@mail.nih.gov and cjki@med.wayne.edu

Abstract

Aims Microbial invasion of the amniotic cavity (MIAC) elicits a fetal inflammatory response such as funisitis and chorionic vasculitis. However, little is known about the changes of fetal skin during MIAC. Toll-like receptors recognize microbial products and initiate an immune response. The aims of this study were to examine histopathological features of fetal skin exposed to MIAC and to assess the changes in Toll-like receptor (TLR)-2 and TLR-4 expression.

Methods and results Skin samples were obtained from fetal autopsies (n = 12). The cases were classified according to the presence (n = 8) or absence (n = 4) of acute chorioamnionitis and analysed by immunohistochemistry using a panel of antibodies. Leucocytic infiltrates into the superficial dermis were observed in cases with chorioamnionitis; the majority of inflammatory cells were neutrophils, lymphocytes and histiocytes. TLR-2 immunoreactivity in the skin was stronger in fetuses with chorioamnionitis than in those without this condition. However, immunoreactivity of TLR-4 in the fetal skin was constitutively expressed, regardless of the presence or absence of chorioamnionitis.

Conclusions This study demonstrates for the first time that fetal dermatitis can be detected and is part of the fetal inflammatory response syndrome (FIRS). We propose that this ‘FIRS-associated fetal dermatitis’ is a fetal counterpart of chorioamnionitis.

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