title: Targeting IL-1β and IL-17A driven inflammation during influenza-induced exacerbations of chronic lung inflammation.
abstract: 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.
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Lausanne, Switzerland; Molecular Biomedicine, ETHZ, Zurich, Switzerland.
authors.forename: Anke
authors.initials: A
authors.lastname: Sichelstiel
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Lausanne, Switzerland.
authors.forename: Koshika
authors.initials: K
authors.lastname: Yadava
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Lausanne, Switzerland.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Trompette
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Lausanne, Switzerland.
authors.forename: Olawale
authors.initials: O
authors.lastname: Salami
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, Tokyo, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Lausanne, Switzerland.
authors.forename: Laurent P
authors.initials: LP
authors.lastname: Nicod
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Lausanne, Switzerland.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Marsland
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use; D002908:Chronic Disease; D006801:Humans; D007251:Influenza, Human / Q000150:complications* / Q000276:immunology / Q000628:therapy; D053590:Interleukin 1 Receptor Antagonist Protein / Q000276:immunology / Q000627:therapeutic use; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000276:immunology / Q000628:therapy; D011014:Pneumonia / Q000150:complications* / Q000276:immunology / Q000628:therapy; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000276:immunology / Q000628:therapy; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D053590:Interleukin 1 Receptor Antagonist Protein; D020381:Interleukin-17; D053583:Interleukin-1beta; D011994:Recombinant Proteins