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Interleukin-11 Receptor Subunit Alpha-1 is Required for Maximal Airway Responsiveness to Methacholine After Acute Exposure to Ozone

Updated June 7, 2023

February 2023
NIOSH Dataset RD-1047-2022-0


Interleukin (IL)-11, a pleiotropic, cationic cytokine, contributes to numerous biological processes, including adipogenesis, hematopoiesis, and inflammation.  Asthma, a chronic respiratory disease, is notably characterized by reversible airway obstruction, persistent lung inflammation, and airway hyperresponsiveness (AHR).  Nasal insufflation of IL-11 causes AHR in wild-type mice while lung inflammation induced by antigen sensitization and challenge, which mimics features of atopic asthma in humans, is attenuated in mice genetically deficient in IL-11 receptor subunit alpha-1 (IL-11Rα1-deficient mice), a transmembrane receptor that is required along with glycoprotein 130 to transduce IL-11 intracellular signaling.  Nevertheless, the contribution of IL-11Rα1 to the manifestation of phenotypic features of non-atopic asthma are not presently known. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11Rα1 would attenuate lung inflammation and increases in airway responsiveness following acute inhalation exposure to ozone, a criteria pollutant and non-atopic asthma stimulus.

Data Collection Methods

  • Through this laboratory-based study, we investigated whether mice genetically deficient in IL-11Rα1 (IL-11Rα1-deficient mice) exhibited decreased airway responsiveness to methacholine and lung inflammation induced by acute inhalation exposure to ozone [2 parts/million (ppm)] for three hours as compared to wild-type (C57BL/6J) mice.
  • Eight- to twenty-week-old wild-type and IL-11Rα1-deficient mice were exposed for three hours to either filtered room air or ozone (2 ppm). Four- or twenty-four-hours following cessation of exposure, one cohort of mice was euthanized so that blood could be collected, a bronchoalveolar lavage (BAL) performed, and lungs harvested.  A second cohort of mice was anesthetized twenty-four-hours following cessation of exposure and pressure-volume (PV) curves generated and airway responsiveness to methacholine assessed.
  • Endpoint measurements include
    • BAL adiponectin, ciliated epithelial cells, hyaluronan, interleukin (IL)-6, IL-11, keratinocyte chemoattractant (KC), macrophage inflammatory protein (MIP)-3α, macrophages, neutrophils, osteopontin, and soluble tumor necrosis factor receptor (sTNFR) 1 and 2
    • Serum IL-11 and sTNFR1 and 2
    • Expression of lung tissue interleukin 11 receptor, alpha chain 1 (Il11ra1) mRNA
    • PV curve parameters: A, an estimate of inspiratory capacity; K, curvature of the upper portion of the expiratory limb of the PV curve; Cstat, quasi-static respiratory system compliance; Area, respiratory system hysteresis
    • Airway responsiveness to methacholine indices: Raw, airway resistance; G, coefficient of lung tissue damping; H, coefficient of lung tissue elastance

Publications Based on Dataset

Johnston RA, Atkins CL, Siddiqui SR, Jackson WT, Mitchell NC, Spencer CY, Pilkington IV, AW, Kashon ML, and Haque IU. Interleukin-11 receptor subunit alpha-1 is required for maximal airway responsiveness to methacholine after acute exposure to ozone. Am J Physiol Regul Integr Comp Physiol 323:R921-R934. DOI: 10.1052/ajpregu.00213.2022.


This work was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under award numbers R03ES022378 and R03ES024883, the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R03AI107432, and the National Institute for Occupational Safety and Health.

When a publication uses this dataset, acknowledgement of the dataset construction should be attributed to the Health Effects Laboratory Division of the National Institute for Occupational Safety and Health.

1National Institute for Occupational Safety and Health,
2University of Texas Health Science Center at Houston,
3Baylor College of Medicine


NIOSH/Health Effects Laboratory Division
Pathology and Physiology Research Branch
(304) 285-5831