title: Comparison of effects of anti-IL-3, IL-5 and GM-CSF treatments on eosinophilopoiesis and airway eosinophilia induced by allergen.
abstract: Allergic inflammation is dominated by eosinophils. IL-3, IL-5, and GM-CSF are involved in production and activation of eosinophils. IL-5 has been reported to be crucial for the induction of airway eosinophilia. However, the contribution of IL-3 and GM-CSF to allergic airway inflammation remains to be determined. To address this issue, ovalbumin-sensitized Balb/c mice were repeatedly exposed to allergen via airway route. Animals were pretreated intraperitoneally with neutralising anti-IL-3, anti-IL-5 and/or anti-GM-CSF antibodies. Newly produced inflammatory cells were pulse-labelled with the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU), which is incorporated into DNA during the cell mitosis. BAL and bone marrow cells were collected 24 h after the last allergen exposure, and differential cell counts and immunocytochemical detection of BrdU-labelled cells were performed. Anti-IL-5 strongly reduced both BAL and bone marrow eosinophilia, as well as the number of BrdU-positive BAL-granulocytes. In contrast, anti-IL-3 and anti-GM-CSF alone had little and no inhibitory effect on these responses, respectively. Even the combined treatment with anti-IL-3 and anti-GM-CSF showed only a non-significant tendency to attenuate these responses. These data suggest that the efficacy of treatments with anti-IL-3 and anti-GM-CSF is much weaker than that with anti-IL-5. IL-5 may be the preferred target to block eosinophilia in allergic diseases.
authors.affiliation: The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Heart and Lung Diseases, Göteborg University, Guldhedsgatan 10A, S-413 46 Gothenburg, Sweden. tomaki@intl.med.tohoku.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tomaki
authors.forename: Lin-Ling
authors.initials: LL
authors.lastname: Zhao
authors.forename: Margareta
authors.initials: M
authors.lastname: Sjöstrand
authors.forename: Anders
authors.initials: A
authors.lastname: Lindén
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
mesh_terms: D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D000963:Antimetabolites / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D004802:Eosinophilia / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D007377:Interleukin-3 / Q000037:antagonists & inhibitors* / Q000276:immunology; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects / Q000276:immunology
chemical_list: D000485:Allergens; D000963:Antimetabolites; D007377:Interleukin-3; D015848:Interleukin-5; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin; D001973:Bromodeoxyuridine