Pathogenesis of murine experimental allergic rhinitis: A study of local and systemic consequences of IL-5 deficiency

Hiroko Saito, Koichiro Matsumoto, Avram E. Denburg, Lynn Crawford, Russ Ellis, Mark D. Inman, Roma Sehmi, Kiyoshi Takatsu, Klaus I. Matthaei, Judah A. Denburg

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

Recent studies have demonstrated an important role for IL-5-dependent bone marrow eosinophil progenitors in allergic inflammation. However, studies using anti-IL-5 mAbs in human asthmatics have failed to suppress lower airway hyperresponsiveness despite suppression of eosinophilia; therefore, it is critical to examine the role of IL-5 and bone marrow responses in the pathogenesis of allergic airway disease. To do this, we studied the effects of IL-5 deficiency (IL-5-/-) on bone marrow function as well as clinical and local events, using an established experimental murine model of allergic rhinitis. Age-matched IL-5+/+ and IL-5-/- BALB/c mice were sensitized to OVA followed by 2 wk of daily OVA intranasal challenge. IL-5-/- OVA-sensitized mice had significantly higher nasal mucosal CD4+ cells and basophilic cell counts as well as nasal symptoms and histamine hyperresponsiveness than the nonsensitized group; however, there was no eosinophilia in either nasal mucosa or bone marrow; significantly lower numbers of eosinophil/basophil CFU and maturing CFU eosinophils in the presence of recombinant mouse IL-5 in vitro; and significantly lower expression of IL-5Rα on bone marrow CD34+CD45+ progenitor cells in IL-5-/- mice. These findings suggest that IL-5 is required for normal bone marrow eosinophilopoiesis, in response to specific Ag sensitization, during the development of experimental allergic rhinitis. However, the results also suggest that suppression of the IL-5-eosinophil pathway in this model of allergic rhinitis may not completely suppress clinical symptoms or nasal histamine hyperresponsiveness, because of the existence of other cytokine-progenitor pathways that may induce and maintain the presence of other inflammatory cell populations.

Original languageEnglish
Pages (from-to)3017-3023
Number of pages7
JournalJournal of Immunology
Volume168
Issue number6
DOIs
Publication statusPublished - Mar 15 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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