IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice

• Published in: PloS one Vol. 12; no. 7; p. e0180690
• Main Authors: Devos, Fien C, Pollaris, Lore, Cremer, Jonathan, Seys, Sven, Hoshino, Tomoaki, Ceuppens, Jan, Talavera, Karel, Nemery, Benoit, Hoet, Peter H M, Vanoirbeek, Jeroen A J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.07.2017; Public Library of Science (PLoS)
• Subjects: Acetone; Allergies; Animals; Antibodies - administration & dosage; Antibodies - pharmacology; Asthma; Asthma - chemically induced; Asthma - drug therapy; Asthma - immunology; Attorneys; Biology and Life Sciences; Cytokines; Development and progression; Disease Models, Animal; Genotype & phenotype; Health aspects; Hypersensitivity; Immunoglobulin E; Immunoglobulin E - blood; Immunology; Inflammation; Interleukin 13; Interleukin-13 - antagonists & inhibitors; Interleukin-13 - genetics; Laboratories; Lymph nodes; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Measurement; Medicine and Health Sciences; Methacholine; Mice; Mice, Inbred C57BL; Mice, Knockout; Oils & fats; Olive oil; Patients; Primary care; Public health; Receiving; Research and Analysis Methods; Respiratory tract; Risk factors; Rodents; Smooth muscle; Toluene; Toluene 2,4-Diisocyanate - adverse effects; Belgium
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0180690

While the importance of the Th2 cytokine IL-13 as a central mediator of airway hyperreactivity (AHR) has been described in allergic protein-induced asthma, this has never been investigated in chemical-induced asthma. We examined the importance of IL-13 in a mouse model of chemical-induced AHR, using toluene-2,4-diisocyanate (TDI). In a first set-up, wild type (WT) and IL-13 knockout (KO) C57Bl/6 mice were dermally treated on days 1 and 8 with 1% TDI or vehicle (acetone/olive oil) on both ears. On day 15, mice received an intranasal instillation with 0.1% TDI or vehicle. In a second set-up, WT mice sensitized with 1% TDI or vehicle, received i.v. either anti-IL-13 or control antibody prior to the intranasal challenge. TDI-sensitized and TDI-challenged WT mice showed AHR to methacholine, in contrast to TDI-sensitized and TDI-challenged IL-13 KO mice, which also showed lower levels of total serum IgE. TDI-sensitized and TDI-challenged IL-13 KO mice had lower numbers of T-cells in the auricular lymph nodes. TDI-treated WT mice, receiving anti-IL-13, showed no AHR, in contrast to those receiving control antibody, despite increased levels of IgE. Anti-IL-13 treatment in TDI-treated WT mice resulted in lower levels of serum IL-13, but did not induce changes in T- and B-cell numbers, and in the cytokine production profile. We conclude that IL-13 plays a critical role in the effector phase of chemical-induced, immune-mediated AHR. This implicates that anti-IL-13 treatment could have a beneficial effect in patients with this asthma phenotype.