IL-10 gene knockout attenuates allergen-induced airway hyperresponsiveness in C57BL/6 mice

• Published in: American journal of physiology. Lung cellular and molecular physiology 2001-02, Vol.280 (2), p.363-L368
• Main Authors: Justice, J. Paul, Shibata, Y, Sur, S, Mustafa, J, Fan, M, Van Scott, M. R
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Allergens - immunology; Animals; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - immunology; Dose-Response Relationship, Drug; Immunoglobulins - blood; In Vitro Techniques; Inflammation - immunology; Inflammation - metabolism; Interleukin-10 - administration & dosage; Interleukin-10 - deficiency; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-13 - analysis; Interleukin-4 - analysis; Interleukin-5 - analysis; Male; Methacholine Chloride; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, SCID; Recombinant Proteins - administration & dosage; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Respiratory Hypersensitivity - chemically induced; Respiratory Hypersensitivity - genetics; Respiratory Hypersensitivity - immunology; Spleen - cytology; Spleen - immunology; Spleen - transplantation; Th2 Cells - immunology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2001.280.2.l363

1  Departments of Physiology and Pharmacology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858; and 2  Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555 Intratracheal administration of interleukin-10 (IL-10) has been reported to inhibit allergic inflammation but augment airway hyperresponsiveness (AHR). In the present study, airway and smooth muscle responsiveness to methacholine (MCh) were compared in wild-type (WT) and IL-10-deficient (IL-10-KO) mice to investigate the role of endogenous IL-10 in AHR development. Naive WT and IL-10-KO mice exhibited similar dose-dependent increases in airway resistance (Raw) to intravenous MCh. Sensitization and challenge with ragweed (RW) induced a twofold increase in responsiveness to intravenous MCh in WT mice, but hyperresponsiveness was not observed in similarly treated IL-10-KO mice. Likewise, tracheal rings from RW-sensitized and -challenged WT mice exhibited a fourfold greater responsiveness to MCh than IL-10-KO tracheal preparations. Measurements of airway constriction by whole body plethysmography further supported the Raw and tracheal ring data (i.e., AHR was not observed in the absence of IL-10). Interestingly, factors previously implicated in the development of AHR, including IL-4, IL-5, IL-13, IgA, IgG1, IgE, eosinophilia, and lymphocyte recruitment to the airways, were upregulated in the IL-10-KO mice. Treatment with recombinant murine IL-10 at the time of allergen challenge reduced the magnitude of inflammation but reinstated AHR development in IL-10-KO mice. Adoptive transfer of mononuclear splenocytes to IL-10-sufficient severe combined immunodeficient mice indicated that lymphocytes were an important source of the IL-10 impacting AHR development. These results provide evidence that IL-10 expression promotes the development of allergen-induced smooth muscle hyperresponsiveness. bronchial hyperresponsiveness; asthma; eosinophilia; interleukin-10