Intravenous anti-IL-5 monoclonal antibody reduces eosinophils and tenascin deposition in allergen-challenged human atopic skin.
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.
Phipps
Simon
S
Department of Allergy and Clinical Immunology, Imperial College London, NHLI Division, London, UK.
Flood-Page
Patrick
P
Menzies-Gow
Andrew
A
Ong
Yee Ean
YE
Kay
A B
AB
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001706:Biopsy; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007275:Injections, Intravenous; D015848:Interleukin-5 / Q000276:immunology*; D008875:Middle Aged; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019063:Tenascin / Q000378:metabolism*
D000485:Allergens; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015848:Interleukin-5; D019063:Tenascin; C434107:mepolizumab