Glucagon-like peptide 1 receptor signaling attenuates respiratory syncytial virus–induced type 2 responses and immunopathology

To the Editor: Glucagon-like peptide 1 receptor (GLP-1R) agonists, which potentiate insulin and suppress glucagon secretion, are a well-accepted and safe treatment for type II diabetes.1 Although GLP-1R agonists are used currently for their endocrine properties, recent evidence suggests that GLP-1R signaling also has anti-inflammatory effects.2-4 Severe respiratory syncytial virus (RSV)–associated illness is in part caused by IL-13 production, which mediates the mucus metaplasia that directly contributes to airway obstruction and respiratory failure.5 We hypothesized that GLP-1R signaling inhibits IL-13–mediated immunopathology of RSV 12/12-6, a strain of RSV that was isolated from a hospitalized infant with severe lower respiratory tract infection and bronchiolitis. GLP-1R agonist treatment in RSV-infected mice significantly decreased numbers of CD4+ T cells and basophils, as well as IL-13+ TH2 cells and basophils, compared with RSV-infected vehicle-treated mice (Fig 1, C and D, and see Fig E3, B and C, and Fig E4, G and H). [...]there were significant decreases in methacholine-induced airway responsiveness and mucus severity scores in RSV-infected GLP-1R agonist–treated mice compared with RSV-infected vehicle-treated mice (Fig 1, F-H). Il33Citrine/+ reporter mice were generated by crossbreeding WT BALB/c mice and Il33Citrine/Citrine mice, which were a kind gift of Dr Andrew N. J. McKenzie.E3 Mice were maintained under specific pathogen-free conditions and used in compliance with the revised 2011 “Guide for the care and use of laboratory animals” prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Research Council.E4 For infection, mice were anesthetized by means of intraperitoneal injection of ketamine/xylazine solution and inoculated through intranasal delivery with 9 × 105 PFU of RSV 12/12-6 or an equal volume of mock inoculum, as previously described.E5 Weight loss was measured daily. Phenotype Cases Control subjects Odds ratio P value Scleritis and episcleritis 67 25,573 2.33 .00006 Alkalosis 187 18,873 1.67 .00032 Acute pharyngitis 798 22,135 1.31 .00051 Acute bronchitis and bronchiolitis 1,223 22,347 1.24 .00063 Postinflammatory pulmonary fibrosis 349 19,926 1.43 .00094 Diabetes mellitus 5,032 21,287 0.88 .00136 Type 1 diabetes 468 21,287 0.67 .00157 Morbid obesity 972 24,650 1.23 .00276 Other forms of chronic heart disease 1,095 21,791 1.22 .00359 Other disorders of male genital