INTERLEUKIN-4, INTERLEUKIN-5, AND INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA IN NORMAL AND ASTHMATIC AIRWAYS - EVIDENCE FOR THE HUMAN MAST-CELL AS A SOURCE OF THESE CYTOKINES

Asthma is characterized by the presence of an inflammatory cell infilt rate in the bronchial mucosa consisting of activated mast cells, eosin ophils, and T cells. Several cytokines are considered to play a pivota l role in this response, particularly interleukin (IL)-4, IL-5, IL-6, and tumor necrosis factor-alpha (TNF-alpha). In this study, we have us ed immunohistochemistry applied to thin glycol methacrylate sections o f bronchial mucosal biopsies to define the cellular provenance of thes e cytokines in normal and asthmatic airways. Both the asthmatic and no rmal mucosa contained numerous cells staining positively for all four cytokines, with the majority identified as mast cells by their tryptas e content. Eosinophils also accounted for some IL-5 immunostaining in the asthmatic biopsies. By using two monoclonal antibodies directed to different epitopes of IL-4, we provide tentative evidence for enhance d IL-4 secretion in asthma. Similarly, a sevenfold increase in the num ber of mast cells staining for TNF-alpha in the asthmatic biopsies sug gests that this cytokine is also up-regulated in this disease. These f indings clearly identify human mast cells as a source of IL-4, IL-5, I L-6, and TNF-alpha and add to the view that, along with T cells, mast cells may play an important role in initiating and maintaining the inf lammatory response in asthma.