Intra-Amniotic IL-1b induces fetal inflammation in rhesus monkeys and alters the regulatory t Cell/IL-17 balance

Suhas G. Kallapur, Pietro Presicce, Paranthaman Senthamaraikannan, Manuel Alvarez, Alice F Tarantal, Lisa Miller, Alan H. Jobe, Claire A. Chougnet

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Very low birth weight preterm newborns are susceptible to the development of debilitating inflammatory diseases, many of which are associated with chorioamnionitis. To define the effects of chorioamnionitis on the fetal immune system, IL-1b was administered intra-Amniotically at ~80% gestation in rhesus monkeys. IL-1b caused histological chorioamnionitis, as well as lung inflammation (infiltration of neutrophils or monocytes in the fetal airways). There were large increases in multiple proinflammatory cytokine mRNAs in the lungs at 24 h postadministration, which remained elevated relative to controls at 72 h. Intra-Amniotic IL-1b also induced the sustained expression of the surfactant proteins in the lungs. Importantly, IL-1b significantly altered the balance between inflammatory and regulatory T cells. Twenty-four hours after IL-1b injection, the frequency of CD3+CD4+FOXP3 + T cells was decreased in lymphoid organs. In contrast, IL-17A-producing cells (CD3+CD4+, CD3+CD42, and CD32CD42 subsets) were increased in lymphoid organs. The frequency of IFN-g-expressing cells did not change. In this model of a single exposure to an inflammatory trigger, CD3+CD4+FOXP3+ cells rebounded quickly, and their frequency was increased at 72 h compared with controls. IL-17 expression was also transient. Interestingly, the T cell profile alteration was confined to the lymphoid organs and not to circulating fetal T cells. Together, these results suggest that the chorioamnionitis-induced IL-1/IL-17 axis is involved in the severe inflammation that can develop in preterm newborns. Boosting regulatory T cells and/or controlling IL-17 may provide a means to ameliorate these abnormalities.

Original languageEnglish (US)
Pages (from-to)1102-1109
Number of pages8
JournalJournal of Immunology
Volume191
Issue number3
DOIs
StatePublished - Aug 1 2013

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Intra-Amniotic IL-1b induces fetal inflammation in rhesus monkeys and alters the regulatory t Cell/IL-17 balance'. Together they form a unique fingerprint.

  • Cite this