Regulatory role of antigen-induced interleukin-10, produced by CD4 + T cells, in airway neutrophilia in a murine model for asthma

Academic Article

Abstract

  • It has been suggested that interleukin (IL)-10 exerts immunosuppressive effects on allergic inflammation, including asthma, mainly through inhibition of Th2 cell-mediated eosinophilic airway inflammation. In a model of experimental asthma utilizing multiple intratracheal antigen challenges in sensitized mice, IL-10 production as well as eosinophilia and neutrophilia in the lung were induced by the multiple challenges. In this study, we set out to reveal the cellular source of endogenously produced IL-10, and the roles of IL-10 in airway leukocyte inflammation using an anti-IL-10 receptor monoclonal antibody. Balb/c mice were sensitized i.p. with ovalbumin + Al(OH) 3, and then challenged by intratracheal administration of ovalbumin 4 times. Flow cytometric analyses revealed that the cellular source of IL-10 was CD4 + T cells lacking the transcription factor, forkhead box P3. Treatment with anti-IL-10 receptor monoclonal antibody prior to the 4th challenge significantly augmented airway neutrophilia as well as the production of IL-1β, and CXC chemokines, keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-2, but not airway eosinophilia, Th2 cytokine (IL-4 and IL-5) production, or a late-phase increase in specific airway resistance. Approximately 40% of IL-10 receptor + cells expressed the macrophage marker F4/80, whereas only 3-4% of the IL-10 receptor + cells were granulocyte differentiation antigen (Gr)-1 high cells (neutrophils). In conclusion, multiple airway antigen challenges induced the proliferation of IL-10-expressing CD4 + T cells in regulating airway neutrophilia. Systemic blockade of IL-10 function coincided with increases in IL-1β and CXC chemokines. Thus, IL-1β and CXC chemokines may be targets for development of novel pharmacotherapy for neutrophilic asthma. © 2011 Elsevier B.V. All rights reserved.
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    Digital Object Identifier (doi)

    Author List

  • Nabe T; Ikedo A; Hosokawa F; Kishima M; Fujii M; Mizutani N; Yoshino S; Ishihara K; Akiba S; Chaplin DD
  • Start Page

  • 154
  • End Page

  • 162
  • Volume

  • 677
  • Issue

  • 1-3