Intravenous anti-IL-5 monoclonal antibody reduces eosinophils and tenascin deposition in allergen-challenged human atopic skin

J Invest Dermatol. 2004 Jun;122(6):1406-12. doi: 10.1111/j.0022-202X.2004.22619.x.

Abstract

Anti-IL-5 monoclonal antibody (mepolizumab) reduces baseline bronchial mucosal eosinophils and deposition of extracellular matrix proteins in the reticular basement membrane in mild asthma. Here we report the effect of anti-IL-5, in the same patients, on allergen-induced eosinophil accumulation, tenascin deposition (as a marker of repair and remodelling) and the magnitude of the late-phase allergic cutaneous reaction. Skin biopsies were performed in 24 atopic subjects at allergen- and diluent-injected sites before 6 and 48 h after, three infusions of a humanized, monoclonal antibody against IL-5 (mepolizumab) using a randomized double-blind, placebo-controlled design. Anti-IL-5 significantly inhibited eosinophil infiltration in 6 h and 48 h skin biopsies as well as the numbers of tenascin immunoreactive cells at 48 h. In contrast, anti-IL-5 had no significant effect on the size of the 6 or 48 h late-phase cutaneous allergic reaction. This study (a) suggests that eosinophils are unlikely to cause the redness, swelling, and induration characteristic of the peak (6 h) late-phase cutaneous allergic reaction and (b) shows that decreases in tenascin positive cells at 48 h correlates with reduction of eosinophils, so providing further evidence of involvement in remodelling processes associated with allergic inflammation.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allergens / administration & dosage
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Biopsy
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / metabolism
  • Dermatitis, Atopic / pathology
  • Eosinophils / immunology
  • Eosinophils / pathology*
  • Humans
  • Injections, Intravenous
  • Interleukin-5 / immunology*
  • Middle Aged
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology
  • Tenascin / metabolism*

Substances

  • Allergens
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin-5
  • Tenascin
  • mepolizumab