INFLAMMATORY DETERMINANTS OF ASTHMA SEVERITY - MEDIATOR AND CELLULAR-CHANGES IN BRONCHOALVEOLAR LAVAGE FLUID OF PATIENTS WITH SEVERE ASTHMA

Cellular and mediator profiles in bronchoalveolar lavage have not been compared systematically between patients with asthma of different sev erities, mainly because the patients with more severe asthma have an i ncreased need for antiinflammatory medication. Information is limited to comparisons of allergic and intrinsic asthma, which can be distingu ished clinically. When patients from these two groups with similar deg rees of bronchial hyperresponsiveness were compared, both groups showe d increased numbers of activated T-helper lymphocytes; those in the al lergic group expressed the IL-2 receptor (C25+) whereas in patients wi th intrinsic asthma there was also an increased number of T-suppressor cells with the activation markers CD25, class II histocompatibility a ntigen, and very late activation antigen-1, as well as T-helper cells class II histocompatibility antigen and very late activation antigen-1 . This pattern is compatible with a more chronic T-cell activation in patients with intrinsic asthma. In patients with allergic asthma the c ytokine pattern is compatible with a pure T-H2 response (elevated IL-4 and IL-5); however intrinsic asthma is characterized by elevated IL-5 and IL-2 but not IL-4. Our own findings show similar concentrations o f IL-1, IL-8, and granulocyte-macrophage colony-stimulating factor in bronchoalveolar lavage fluid of patients with allergic and intrinsic a sthma, whereas IL-6 and interferon-gamma tended to be higher in patien ts with intrinsic asthma. There are probably fundamental differences i n the pathogenesis of allergic and intrinsic asthma. These findings su ggest that asthma does not depend on the presence of IgE or IL-4, alth ough both may contribute to the pathogenesis of atopic asthma. The onl y common pathway in the different presentations of asthma that has bee n related to clinical symptoms appears to be IL-5-mediated activation of eosinophils; therapies aimed at this mechanism may be promising.