Comparison of effects of anti-IL-3, IL-5 and GM-CSF treatments on eosinophilopoiesis and airway eosinophilia induced by allergen

Pulm Pharmacol Ther. 2002;15(2):161-8. doi: 10.1006/pupt.2001.0333.

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.

Publication types

  • Comparative Study

MeSH terms

  • Allergens / adverse effects*
  • Animals
  • Antimetabolites / metabolism
  • Bone Marrow / drug effects*
  • Bone Marrow / metabolism
  • Bromodeoxyuridine / metabolism
  • Bronchoalveolar Lavage Fluid
  • Eosinophilia / drug therapy*
  • Eosinophilia / etiology
  • Eosinophilia / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Interleukin-3 / antagonists & inhibitors*
  • Interleukin-3 / immunology
  • Interleukin-5 / antagonists & inhibitors*
  • Interleukin-5 / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / adverse effects
  • Ovalbumin / immunology

Substances

  • Allergens
  • Antimetabolites
  • Interleukin-3
  • Interleukin-5
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Ovalbumin
  • Bromodeoxyuridine