Chronic eosinophilic pneumonia is a progressive pulmonary disorder characterized by dyspnea, evening fever, night sweats, weight loss, a widened alveolar-arterial gradient for oxygen, a characteristic chest radiographic, and bronchoalveolar lavage (BAL) fluid eosinophilia. The agent(s) responsible for this disorder have not been defined. Because we have noted hypodense eosinophils and increased levels of interleukin 5 in the sera of patients with the idiopathic hypereosinophilic syndrome and tryptophan-associated eosinophilia-myalgia syndrome, we postulate that in chronic eosinophilic pneumonia, the eosinophils are rendered long-lived and become functionally primed by exposure to one or more specific regulatory cytokines. Either in parallel, or as a subsequent event, the eosinophils localize to the pulmonary parenchyma in relation to the source of the cytokine, or in response to an independent concurrent stimulus. It is established that eosinophil phenotype is an index of cytokine exposure and priming in vivo. Based upon this finding, density gradient sedimentation will be used to separate peripheral blood eosinophils from patients with chronic eosinophilic pneumonia into normodense and hypodense subpopulations. The separated cells will be phenotyped based upon ex vivo survival, quantitative LTC4 generation, cytotoxicity, and membrane expression of selected complement and immunoglobulin receptors and adhesion molecules. Eosinophils in BAL fluid will be phenotyped based upon density and ex vivo survival. Serum and BAL fluid will be assessed for their capacity to maintain eosinophil viability and regulated their phenotype. If cytokine-like activities are present, they will be characterized based upon immunologic determinants and, to the extent possible, chromatographically. If such factors are present in the acute phase of the disease, they will be reexamined after the induction of a remission. Lastly, to determine the cell source of these putative eosinophil regulatory cytokines, T lymphocytes in peripheral blood and BAL fluid, and lung tissue sections will be examined by RNA blot analysis and in situ hybridization for alterations in mRNA expression of relevant cytokines. After the induction of a clinical remission, the cytokine profile from relevant lymphocyte populations will be repeated.
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