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 bronchial tissue of asthmatic patients and related this to the clinical and functional characteristics. Patients were allocated into two different groups on the basis of their atopic status (atopic and nonatopic), with two subgroups of symptomatic and asymptomatic subjects in each. Five healthy volunteers were tested as control subjects. After clinical and functional assessment, all of the subjects underwent bronchoscopy. Several biopsy specimens were obtained for immunohistochemical and immunoelectron 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 asymptomatic patients or normal control subjects. The cell sources of IL-1 beta were monocytes and dendritic cells in atopic patients and monocytes alone in nonatopic asthmatic subjects. The CD4+ T lymphocytes from atopic asthmatic subjects predominantly expressed IL-3, IL-4, IL-5, and GM-CSF immunoreactivity, whereas CD4+ T cells from nonatopic patients predominantly expressed IL-2, IL-3, and IL-5, and GM-CSF immunoreactivity. 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 the 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.