title: Pathogenesis of murine experimental allergic rhinitis: a study of local and systemic consequences of IL-5 deficiency.
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-5Ralpha 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.
authors.affiliation: Asthma Research Group, Division of Clinical Immunology and Allergy, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Saito
authors.forename: Koichiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Avram E
authors.initials: AE
authors.lastname: Denburg
authors.forename: Lynn
authors.initials: L
authors.lastname: Crawford
authors.forename: Russ
authors.initials: R
authors.lastname: Ellis
authors.forename: Mark D
authors.initials: MD
authors.lastname: Inman
authors.forename: Roma
authors.initials: R
authors.lastname: Sehmi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.forename: Klaus I
authors.initials: KI
authors.lastname: Matthaei
authors.forename: Judah A
authors.initials: JA
authors.lastname: Denburg
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D001491:Basophils / Q000473:pathology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006632:Histamine / Q000008:administration & dosage; D015848:Interleukin-5 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D008747:Methylcellulose / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053649:Receptors, Interleukin-5; D012221:Rhinitis, Allergic, Perennial / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology
chemical_list: D018952:Antigens, CD34; D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D006632:Histamine; D008747:Methylcellulose; D010047:Ovalbumin; D017493:Leukocyte Common Antigens