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Thorax. 2013 Aug;68(8):717-23. doi: 10.1136/thoraxjnl-2012-202404. Epub 2013 Feb 19.

IL-17A inhibits airway reactivity induced by respiratory syncytial virus infection during allergic airway inflammation.

Author information

1
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. dawn.newcomb@vanderbilt.edu

Abstract

BACKGROUND:

Viral infections are the most frequent cause of asthma exacerbations and are linked to increased airway reactivity (AR) and inflammation. Mice infected with respiratory syncytial virus (RSV) during ovalbumin (OVA)-induced allergic airway inflammation (OVA/RSV) had increased AR compared with OVA or RSV mice alone. Furthermore, interleukin 17A (IL-17A) was only increased in OVA/RSV mice.

OBJECTIVE:

To determine whether IL-17A increases AR and inflammation in the OVA/RSV model.

METHODS:

Wild-type (WT) BALB/c and IL-17A knockout (KO) mice underwent mock, RSV, OVA or OVA/RSV protocols. Lungs, bronchoalveolar lavage (BAL) fluid and/or mediastinal lymph nodes (MLNs) were harvested after infection. Cytokine expression was determined by ELISA in the lungs or BAL fluid. MLNs were restimulated with either OVA (323-229) peptide or RSV M2 (127-135) peptide and IL-17A protein expression was analysed. AR was determined by methacholine challenge.

RESULTS:

RSV increased IL-17A protein expression by OVA-specific T cells 6 days after infection. OVA/RSV mice had decreased interferon-β protein expression compared with RSV mice. OVA/RSV mice had increased IL-23p19 mRNA expression in lung homogenates compared with mock, OVA or RSV mice. Unexpectedly, IL-17A KO OVA/RSV mice had increased AR compared with WT OVA/RSV mice. Furthermore, IL-17A KO OVA/RSV mice had increased eosinophils, lymphocytes and IL-13 protein expression in BAL fluid compared with WT OVA/RSV mice.

CONCLUSIONS:

IL-17A negatively regulated AR and airway inflammation in OVA/RSV mice. This finding is important because IL-17A has been identified as a potential therapeutic target in asthma, and inhibiting IL-17A in the setting of virally-induced asthma exacerbations may have adverse consequences.

KEYWORDS:

Allergic lung disease; Asthma; Cytokine Biology; Respiratory Infection

PMID:
23422214
PMCID:
PMC3916091
DOI:
10.1136/thoraxjnl-2012-202404
[Indexed for MEDLINE]
Free PMC Article

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