DETECTION OF CYTOKINES AND THEIR CELL SOURCES IN BRONCHIAL BIOPSY SPECIMENS FROM ASTHMATIC-PATIENTS - RELATIONSHIP TO ATOPIC STATUS, SYMPTOMS, AND LEVEL OF AIRWAY HYPERRESPONSIVENESS

This study evaluated immunoreactivity for several cytokines in bronchi al tissue of asthmatic patients and related this to the clinical and f unctional characteristics. Patients were allocated into two different groups on the basis of their atopic status (atopic and nonatopic), wit h two subgroups of symptomatic and asymptomatic subjects in each. Five healthy volunteers were tested as control subjects. After clinical an d functional assessment, all of the subjects underwent bronchoscopy. S everal biopsy specimens were obtained for immunohistochemical and immu noelectron microscopic evaluation. Symptomatic asthmatic subjects had increased expression of immunoreactive interleukin (IL) I beta, IL-2, IL-3, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF alpha) when compared to the asym ptomatic patients or normal control subjects. The cell sources of IL-1 beta were monocytes and dendritic cells in atopic patients and monocy tes alone in nonatopic asthmatic subjects. The CD4+ T lymphocytes from atopic asthmatic subjects predominantly expressed IL-3, IL-4, IL-5, a nd GM-CSF immunoreactivity, whereas CD4+ T cells from nonatopic patien ts predominantly expressed IL-2, IL-3, and IL-5, and GM-CSF immunoreac tivity. Mast cells showed immunoreactivity for TNF alpha, IL-3, IL-5, and GM-CSF. Immunostaining for TNF alpha and GM-CSF was also detected in bronchial epithelial cells and monocytes. Tissue eosinophilia and t he level of airway hyperresponsiveness more closely correlated with IL -5 immunoreactivity in atopic asthmatic subjects and with IL-2 and GM- CSF immunoreactivity in nonatopic patients.