Bronchoalveolar lavage (BAL) leukocyte-secreted cytokines are considered to be important mediators of the inflammatory and allergic reactions in the lung. This study examines quantitative changes in the level of tumor necrosis factor-alpha (TNFa) and interferon-gamma (IFNI') production in BAL cell cultures derived from patients (n= 11) with bronchial asthma. The secretion of TNFa and IFNI'was determined in intact (unstimulated) and phytohemagglutinin/phorbol myristate acetate (PHA+ PMA)-stimulated BAL leukocyte cultures and compared with that in control cultures. In all patients studied, the background and PHA+ PMA-induced secretion of TNFa and IFNI'was significantly (p< 0.001) higher than that in parallel control cultures. In contrast to BAL cell preparations, the capacity of TNFa and IFNI'secretion by patients' peripheral blood mononuclear cells (PBMC) did not differ from that of control subjects. High spontaneous release of TNFa and IFNI'by patients' BAL leukocytes, but not PBMC, suggest that in the pathophysiology of bronchial asthma, these cytokines may act as local pathogenic agents in the lung.

Pathologic changes in bronchial asthma are associated with activation of eosinophils and neutrophils by eosinophil-activating factor (EAF), granulocyte/monocyte-colony-stimulating factor (GM-CSF), or interferon gamma (IFNy), which facilitate these cell infiltrations into the site of allergic reaction (1-4). The influx of inflammatory cells to the lung (1, 2) suggests that the development of the inflammatory reaction in the bronchi may be associated with the in situsecretion of proinflammatory cytokines. The pleiotropic, immunoregulatory mediator such as tumor necrosis factor-alpha (TNFa) can also amplify the inflammatory response by its capacity to enhance eosinophil cytotoxicity (5). Although TNFa and IFNI'can interact in a variety of systems to modulate the immune functions (6, 7), the precise role of TNFa or IFNI'in the pathology of immunologic reactions in the bronchial asthma patient is presently unknown. The existing reports on the secretion of TNFa or IFN (s) by peripheral blood leukocyte cultures from patients with bronchial asthma demonstrate a lack or reduced production of these cytokines in the majority of subjects examined (8-11). However, the development of the pulmonary immune response in bronchial asthma may involve activation of the local lymphoid tissue. Because bronchoalveolar leukocytes are directly exposed to external antigens, an immediate synthesis and/or release of immunomodulatory mediators can occur. In recent studies, Gosset and coworkers (12) indeed demonstrated that the late asthmatic reaction is associated with IgE-dependent secretion of TNFa