title: IL-13 mRNA and immunoreactivity in allergen-induced rhinitis: comparison with IL-4 expression and modulation by topical glucocorticoid therapy.
abstract: The allergen-induced late nasal response (LNR) is associated with high expression of interleukin-4 (IL-4) and IL-5 messenger RNA (mRNA) in the nasal mucosa, suggesting a role for Th2-type cytokines in the development of the LNR. Moreover, topical corticosteroid-mediated inhibition of the LNR is accompanied by inhibition of IL-4, but not IL-5, mRNA expression, IL-13 shares a number of functions with IL-4, including IgE switching and vascular cell adhesion molecule-1 (VCAM-1) upregulation. We investigated the expression of IL-13 mRNA and immunoreactivity in nasal biopsies from 10 normal subjects and 20 subjects with allergic rhinitis. IL-4 mRNA expression was examined in the same subjects. The allergic rhinitis patients were randomized to receive a 6-wk treatment with either topical fluticasone propionate (n = 10) or placebo (n = 10) nasal spray twice daily. A nasal biopsy was taken before treatment and 24 h after local nasal allergen provocation with a grass-pollen extract. Before treatment, there was no significant difference between the allergic rhinitis patients and controls in the expression of IL-13 mRNA and immunoreactivity. After allergen provocation, we observed a significant increase in IL-13 mRNA-positive and immunoreactive cells at 24 h only in subjects given placebo (P < 0.001). Inhibition of the LNR after corticosteroid treatment was associated with a marked decrease in allergen-induced IL-13 mRNA-positive (P < 0.001) and immunoreactive cells (P < 0.001). In subjects given placebo, 76.9 +/- 5.5% of IL-13 mRNA-positive cells observed after allergen were CD3+, whereas 11.2 +/- 2.7% coexpressed immunoreactivity for mast-cell tryptase. In these subjects, increases in cells expressing IL-13 mRNA were greater than for IL-4 mRNA (P = 0.001), and double in situ hybridization studies revealed that 100% of the IL-4 mRNA-positive cells coexpressed IL-13 mRNA, whereas 66.6 +/- 10.5% of IL-13 mRNA-positive cells coexpressed IL-4 transcripts after allergen challenge. The results of this study suggest that IL-13 expression is a prominent feature of the LNR, and that inhibition of the LNR following steroid therapy may be partly attributable to inhibition of IL-13 expression.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Canada.
authors.forename: O
authors.initials: O
authors.lastname: Ghaffar
authors.forename: S
authors.initials: S
authors.lastname: Laberge
authors.forename: M R
authors.initials: MR
authors.lastname: Jacobson
authors.forename: O
authors.initials: O
authors.lastname: Lowhagen
authors.forename: S
authors.initials: S
authors.lastname: Rak
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000485:Allergens; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001706:Biopsy; D017252:CD3 Complex / Q000032:analysis; D053818:Chymases; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008297:Male; D008407:Mast Cells / Q000201:enzymology; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D010919:Placebos; D012333:RNA, Messenger / Q000096:biosynthesis*; D012016:Reference Values; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology*; D012697:Serine Endopeptidases / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D053802:Tryptases
chemical_list: D000485:Allergens; D000730:Androstadienes; D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D017252:CD3 Complex; D005938:Glucocorticoids; D018793:Interleukin-13; D010919:Placebos; D012333:RNA, Messenger; D015847:Interleukin-4; D000068298:Fluticasone; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases