title: Mucosal inflammation in severe glucocorticoid-dependent asthma.
abstract: To improve our understanding of the inflammatory mechanisms underlying severe disease, a biopsy study was performed comparing 15 clinically unstable glucocorticoid-dependent asthmatics, 10 mild asthmatics, and 10 control subjects. Compared with mild asthma, severe asthma was characterized by reduced mucosal eosinophilia. Whilst no significant differences were found in the numbers of mast cells, neutrophils, CD3+ and CD4+ T-cells between the three groups, up to a 4-fold increase In the numbers of activated T-lymphocytes bearing the interleukin (IL)-2 receptor (IL-2R) was found in the mucosa in severe asthma compared to mild asthma (p = 0.03) and control subjects (p = 0.003). Compared to control subjects, the mucosa of severe asthmatics contained significantly (p = 0.02) higher numbers of IL-5+ cells, with no differences between mild and severe disease. In contrast, staining for the anti-IL-4 monoclonal antibody 3H4 revealed that biopsies from mild asthmatics contained more IL4+ cells than biopsies from severe asthmatics and control subjects (p = 0.0008). In the severe asthmatics, a close correlation (r(s) = 0.76, p = 0.005) was found between the numbers of IL-2R-bearing cells and the variability in peak expiratory flow. In conclusion, persistent T-cell activation is a prominent feature of severe asthma. These results also indicate that interleukin-5, and not interleukin-4, is upregulated in severe disease.
authors.affiliation: Dutch Asthma Centre, Davos, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Vrugt
authors.forename: S
authors.initials: S
authors.lastname: Wilson
authors.forename: J
authors.initials: J
authors.lastname: Underwood
authors.forename: A
authors.initials: A
authors.lastname: Bron
authors.forename: R
authors.initials: R
authors.lastname: de Bruyn
authors.forename: P
authors.initials: P
authors.lastname: Bradding
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: R
authors.initials: R
authors.lastname: Djukanovic
authors.forename: R
authors.initials: R
authors.lastname: Aalbers
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D001980:Bronchi / Q000473:pathology*; D019819:Budesonide / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D002452:Cell Count; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume; D005938:Glucocorticoids; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D010366:Peak Expiratory Flow Rate; D011239:Prednisolone / Q000627:therapeutic use; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000145:classification
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D015848:Interleukin-5; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007073:Immunoglobulin E; D019819:Budesonide; D011239:Prednisolone