Integrated Signals Between IL-13, IL-4, and IL-5 Regulate Airways Hyperreactivity

• Published in: The Journal of immunology (1950) 2000-07, Vol.165 (1), p.108-113
• Main Authors: Webb, Dianne C, McKenzie, Andrew N. J, Koskinen, Aulikki M. L, Yang, Ming, Mattes, Joerg, Foster, Paul S
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - deficiency; Adjuvants, Immunologic - genetics; Adjuvants, Immunologic - physiology; Animals; Bronchial Hyperreactivity - etiology; Bronchial Hyperreactivity - genetics; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - metabolism; Cytokines - biosynthesis; Immune Sera - pharmacology; Interleukin-13 - deficiency; Interleukin-13 - genetics; Interleukin-13 - physiology; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - immunology; Interleukin-4 - physiology; Interleukin-5 - antagonists & inhibitors; Interleukin-5 - immunology; Interleukin-5 - physiology; Interleukins - antagonists & inhibitors; Interleukins - genetics; Interleukins - immunology; Interleukins - physiology; Lymph Nodes - immunology; Lymph Nodes - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Pulmonary Eosinophilia - genetics; Pulmonary Eosinophilia - immunology; Pulmonary Eosinophilia - prevention & control; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism; Respiratory Mucosa - pathology; Signal Transduction - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.1.108

In this investigation, we have examined the integrated relationship between IL-13, IL-4, and IL-5 for the development of airways hyperreactivity (AHR) in a model of asthma in BALB/c mice. Sensitization and aeroallergen challenge of both wild-type (WT) and IL-13 gene-targeted (IL-13-/-) mice induced allergic disease that was characterized by pulmonary eosinophilia and AHR to beta-methacholine. Although these responses in IL-13-/- mice were heightened compared with WT, they could be reduced to the level in nonallergic mice by the concomitant neutralization of IL-4. Mice in which both IL-4 and IL-13 were depleted displayed a marked reduction in tissue eosinophils, despite the development of a blood eosinophilia. Similar neutralization of IL-4 in WT mice only partially reduced AHR with no effect on tissue eosinophilia. In addition, neutralization of IL-5 in IL-13-/- mice, but not in WT mice, inhibited AHR, suggesting that tissue eosinophilia is linked to the mechanism underlying AHR only in the absence of IL-13. Additionally, mucus hypersecretion was attenuated in IL-13-/- mice, despite the persistence of AHR. Taken together, our data suggest both a modulatory role for IL-13 during sensitization and a proinflammatory role during aeroallergen challenge. The latter process appears redundant with respect to IL-4.