Targeting IL-1β and IL-17A Driven Inflammation during Influenza-Induced Exacerbations of Chronic Lung Inflammation

For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and...

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Published in:PloS one Vol. 9; no. 6; p. e98440
Main Authors: Sichelstiel, Anke, Yadava, Koshika, Trompette, Aurélien, Salami, Olawale, Iwakura, Yoichiro, Nicod, Laurent P., Marsland, Benjamin J.
Format: Journal Article
Language:English
Published: United States Public Library of Science 11.06.2014
Public Library of Science (PLoS)
Subjects:
Animals
Antibodies, Neutralizing - immunology
Antibodies, Neutralizing - therapeutic use
Bacterial infections
Biology
Biology and Life Sciences
Bronchitis
Chronic Disease
Chronic obstructive pulmonary disease
Cytokines
Emphysema
Humans
Infections
Inflammation
Influenza
Influenza, Human - complications
Influenza, Human - immunology
Influenza, Human - therapy
Interleukin
Interleukin 1
Interleukin 1 Receptor Antagonist Protein - immunology
Interleukin 1 Receptor Antagonist Protein - therapeutic use
Interleukin-17 - antagonists & inhibitors
Interleukin-17 - immunology
Interleukin-1beta - antagonists & inhibitors
Interleukin-1beta - immunology
Leukocytes (neutrophilic)
Lung diseases
Medicine
Medicine and Health Sciences
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neutrophil Infiltration
Neutrophilia
Neutrophils
Obstructive lung disease
Orthomyxoviridae Infections - complications
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - therapy
Pneumonia - complications
Pneumonia - immunology
Pneumonia - therapy
Pulmonary Disease, Chronic Obstructive - complications
Pulmonary Disease, Chronic Obstructive - immunology
Pulmonary Disease, Chronic Obstructive - therapy
Recombinant Proteins - immunology
Recombinant Proteins - therapeutic use
Recruitment
Rodents
Therapeutic applications
Viral infections
Switzerland
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are key mediators of neutrophilic inflammation in influenza-induced exacerbations of chronic lung inflammation. Using a mouse model of disease, our data shows a role for IL-1β in mediating lung dysfunction, and in driving neutrophilic inflammation during the whole phase of viral infection. We further report a role for IL-17A as a mediator of IL-1β induced neutrophilia at early time points during influenza-induced exacerbations. Blocking of IL-17A or IL-1 resulted in a significant abrogation of neutrophil recruitment to the airways in the initial phase of infection or at the peak of viral replication, respectively. Therefore, IL-17A and IL-1β are potential targets for therapeutic treatment of viral exacerbations of chronic lung inflammation.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: AS BJM LN. Performed the experiments: AS KY AT OS. Analyzed the data: AS KY AT OS. Contributed reagents/materials/analysis tools: YI. Wrote the paper: AS BJM KY.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0098440