MITE ANTIGEN-INDUCED IL-4 AND IL-13 PRODUCTION BY BASOPHILS DERIVED FROM ATOPIC ASTHMA PATIENTS

Background. There is increasing evidence for the role of basophils in the pathogenesis of atopic diseases such as bronchial asthma, atopic d ermatitis and atopic rhinitis. Recently, it has been reported that bas ophils derived from healthy donors produce the immunoregulatory cytoki nes interleukin (IL)-4 and IL-13 after cross-linking of cell surface I gE. In addition to well-known inflammatory mediators, such as histamin e and leukotriene C-4, these cytokines produced by basophils are also considered to be associated with atopic diseases. Objective. Our first objective was to determine whether or not mite-sensitive atopic asthm atic basophils produce IL-4 and IL-13 in response to mite antigens. Ou r second objective was to investigate the relationship between antigen -specific or nonspecific IgE in the serum and the production of these cytokines in order to determine the association of basophil-derived cy tokines with the pathogenesis of atopic asthma. Our final objective wa s to study how production of these cytokines could be regulated by som e anti-asthma drugs. Methods. Basophils were purified from peripheral venous blood of 67 atopic asthma patients with elevated RAST for the h ouse dust mite. Cells were stimulated with mite antigens for 6 hours a nd then IL-4 and IL-13 levels in the supernatants were measured by enz yme-linked immunosorbent assay (ELISA). Results. Mite-sensitive asthma tic basophils produced IL-4 and IL-13 when stimulated with mite antige ns. Mite-induced IL-4 production peaked at 6 hours after the stimulati on, whereas IL-13 production continued up to 24 hours. The higher the concentration of mite specific IgE but not total IgE released in the s erum, the more IL-4 and IL-13 were produced by basophils in response t o mite antigens. The production of these cytokines was significantly s uppressed by the anti-asthma drugs theophylline (IL-4, p < 0.001, n = 6; IL-13, p < 0.001, n = 10) and dexamethasone (IL-4, p < 0.001, n = 1 5; IL-13, p < 0.001, n = 10). Conclusion. Mite-antigen-induced IL-4 an d IL-13 production by basophils derived from mite-sensitive asthma pat ients was associated with the concentration of mite-specific IgE and m ay play an important role in the pathogenesis of atopic asthma. The in hibitory effect of dexamethasone and theophylline on allergic inflamma tion may be due to the inhibition of IL-4 and IL-13 production not onl y by T cells but also by basophils.