NEW INSIGHTS INTO THE PATHOGENESIS OF SEVERE CORTICOSTEROID-DEPENDENTASTHMA

Severe asthma is characterized by persistent T-cell activation, as dem onstrated in both peripheral blood and bronchial mucosa. Endobronchial biopsy specimens of patients with severe, corticosteroid-dependent as thma revealed increased expression of CD25+ on mucosal T cells. Increa sed immunoreactivity, for IL-5 further supports the evidence that the inflammatory response is orchestrated by T-H2-type T cells. Peripheral blood eosinophils and total serum IgE levels were increased in the ab sence of allergen and despite optimal treatment. The chemokine IL-8 ma y also be an aggravating factor in severe asthma; as well as being a p otent chemotactic and activating factor for neutrophils, it may also b e chemoattractant for eosinophils. We have recently detected increased levels of free IL-8 in the peripheral blood of patients with chronic severe asthma but not in healthy control subjects or in patients with mild asthma, even after allergen challenge. In patients with severe as thma there may be an imbalance between IL-8 production and the blockin g capacity of IL-S autoantibodies. Higher levels of IL-8 complexed to IgA autoantibody and increased numbers of activated T cells were also found in patients with unstable asthma compared with patients who had severe but stable disease. We conclude that IL-8 may provide an additi onal marker of asthma severity and corticosteroid responsiveness.