Different roles of interleukin-10 in onset and resolution of asthmatic responses in allergen-challenged mice

• Published in: Respirology (Carlton, Vic.) Vol. 10; no. 1; pp. 18 - 26
• Main Authors: MATSUMOTO, Koichiro, INOUE, Hiromasa, TSUDA, Miyuki, HONDA, Yasuko, KIBE, Atsuko, MACHIDA, Kentaro, YOSHIURA, Yuki, NAKANISHI, Yoichi
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Science Pty 01-01-2005
• Subjects: airway hyperresponsivenes; Allergens - adverse effects; Animals; Antibodies - immunology; asthma; Asthma - immunology; Asthma - physiopathology; Bronchi - immunology; Bronchial Hyperreactivity - immunology; Bronchoalveolar Lavage Fluid - immunology; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; eosinophil; Eosinophils - immunology; Immunization; interleukin-10; Interleukin-10 - immunology; Interleukin-5 - immunology; Male; Mice; Mice, Inbred BALB C; mouse; Ovalbumin - adverse effects; T-Lymphocyte Subsets - immunology; Time Factors
• ISSN: 1323-7799; 1440-1843
• DOI: 10.1111/j.1440-1843.2005.00647.x

Objective:  Although interleukin (IL)‐10 is an immunoregulatory cytokine produced by various cells including T cells, its precise role in asthma remains uncertain. The aim of this study was to investigate the role of IL‐10 in experimental asthma using ovalbumin (OVA)‐sensitized mice.
Methodology:  Mice were challenged with OVA aerosol, and airway responsiveness and inflammation were measured. OVA‐specific IL‐10‐producing CD4+ T cells were counted from lung cells collected by enzymatic digestion and stimulated ex vivo with OVA. The effects of an anti‐IL‐10 antibody on airway responsiveness and inflammation were also evaluated.
Results:  The OVA challenge caused airway hyperresponsiveness and eosinophilic inflammation. A significant increase in IL‐10‐producing CD4+ T cells was observed, mainly in the CD45RBlow subset, for several days after the OVA challenge. Anti‐IL‐10 antibody treatment before the OVA challenge did not affect eosinophilic inflammation but significantly inhibited airway hyperresponsiveness 24 h after the OVA challenge. However, anti‐IL‐10 antibody treatment just before the last OVA challenge significantly attenuated the resolution of eosinophilic inflammation without affecting airway responsiveness 2 weeks after the OVA challenge.
Conclusions:  Intrinsic IL‐10 may have a distinct role in the early and late phases of asthmatic responses. In the early phase, IL‐10 induces airway hyperresponsiveness, while in the late phase IL‐10 contributes to the resolution of eosinophilic inflammation.