The Role of Cytokines in the Pathogenesis of Bronchial Asthma.

Abstract

Inflammatory reactions in the airway in which various inflammatory cells are involved play an important role in the pathogenesis of bronchial asthma. In particular, the activation of T cells and the accompanying role of cytokines have attracted attention. We employed peripheral mononuclear blood cells and lymphocytes from mite-antigen positive patients with bronchial asthma to investigate the production of various cytokines following stimulation with mite-antigen and the relationship between IgE-the most important factor in the pathogenesis of bronchial asthma- and cytokines.The production of IL-1β, IL-2, sIL-2R, IL-3, IL-4, IL-5 and IL-6 from peripheral blood mononuclear cells (PBMC) following the addition of mite-antigen was determined by the sandwich ELISA method. The production of IL-1β, IL-2, sIL-2R, IL-3, IL-4, IL-5 and IL-6 in PBMCs was increased by stimulation with mite-antigen. When CD4+ and CD8+-enriched cell fractions were separated, the production of the cytokines IL-2, sIL-2R and IL-4 was elevated in the CD4+ T cells. IL-1β production from PBMCs increased in the presence of the CD4+-enriched cell fractions. Consequently, the effect of CD4+-enriched cell fractions in the production of IL-1β in mononuclear cells was considered.The results of a determination of IgE production from PBMCs, using a highly-sensitive method, showed that IgE production increased following the addition of IL-4 to a level similar to that induced by stimulation with mite-antigen. The addition of either IFN-γ or anti-IL-4 reduced the amount of IgE increased by the addition of IL-4 or stimulation with mite-antigen. The addition of IL-2 further increased the amount of IgE production, which had been increased by stimulation with mite-antigen or the addition of IL-4, suggesting the importance of IL-2 in IgE production in B cells.The results of our study indicate that mononuclear cells and lymphocytes, especially CD4+ T cells, are important for the onset of bronchial asthma as a Type I allergy.In patients with bronchial asthma, CD4-positive T-lymphocytes are activated, and various cytokines are produced, following stimulation of PBMC with specific antigens. It is suggested that IL-4 and IL-2, which promote the production of IgE-the most important factor in I-type allergic reactions, might produce serious allergic reactions.It is also concluded that the production of IL-3 and IL-5, which are considered to be cytokines activating eosinophils, is increased by stimulation with specific antigens which are potent inducers of further airway inflammation.The above results suggest that various cytokines play an important role in the pathogenesis of bronchial asthma in their interactions with each other.