Mucosal inflammation in severe glucocorticoid-dependent asthma


B. Vrugt
Martini Hospital Groningen
Department of Pathology
PO Box 30033
9700 RM Groningen
The Netherlands
Fax: 31 505245759


To improve our understanding of the inflammatory mechanisms undererlying 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 IL-4+ cells than biopsies from severe asthmatics and control subjects (p=0.0008). In the severe asthmatics, a close correlation (rs=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.