Mucosal inflammation in severe glucocorticoid-dependent asthma

To improve our understanding of the inflammatory mechanisms under-erlying s evere disease, a biopsy study was performed comparing 15 clinically unstabl e glucocorticoid-dependent asthmatics, 10 mild asthmatics, and 10 control s ubjects, Compared with mild asthma, severe asthma was characterized by reduced mucos al eosinophilia. Whilst no significant differences were found in the number s of mast cells, neutrophils, CD3+ and CD4+ T-cells between the three group s, up to a 4-fold increase in the numbers of activated T-lymphocytes bearin g 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 (0.003). Comp ared to control subjects, the mucose of severe asthmatics contained signifi cantly (p=0.02) higher numbers of IL-5+ cells,,vith 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 IL -4+ cells than biopsies from severe asthmatics and control subjects (p=0.00 08), In the severe asthmatics, a close correlation (r(s)=0.76, p=0.0008) wa s found between the numbers of IL-2R-bearing cells and the variability in p eak expiratory flow. In conclusion, persistent T-cell activation is a prominent feature of sever e asthma, These results also indicate that interleukin-5, and not interteuk in-4, is upregulated in severe disease.