title: Tumor-induced eosinophilia and endocardial fibrosis: evidence for ectopic eosinophilopoietin production and toxic O2 metabolite-mediated endothelial damage.
abstract: We have described a patient with the clinical triad of anaplastic pulmonary carcinoma, extreme eosinophilia, and endocardial damage, with resulting fibrosis and mural "thrombosis." Since the "thrombi" consisted mainly of masses of aggregated eosinophils in close approximation to areas of fibrotic cardiac endothelium, it was hypothesized that eosinophils might provoke endothelial damage. Indeed, eosinophils generated large amounts of toxic oxygen species and were highly toxic to cultured endothelial cells in vitro; moreover, high concentrations of corticosteroids inhibited in tandem these phenomena. In addition, from the patient's tumor a 45,000-dalton "eosinophilopoietin" was extracted which stimulated eosinophil colonies without help from T-lymphocytes. We believe our results help explain both the hypereosinophilia which accompanies certain anaplastic carcinomas and the endocardial damage with thrombosis and embolization which may occur in any patient with excessive eosinophils. In this latter regard, our studies suggest that very high doses of corticosteroids--since they decrease generation of toxic oxygen products by, and the numbers of, eosinophils--may be rational therapy in hypereosinophilic syndromes.
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000150:complications*; D004699:Endocardium / Q000473:pathology*; D004727:Endothelium / Q000473:pathology; D004802:Eosinophilia / Q000150:complications / Q000209:etiology*; D006331:Heart Diseases / Q000209:etiology / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000150:complications*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010452:Peptide Biosynthesis; D010455:Peptides; D013927:Thrombosis / Q000209:etiology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C015851:eosinophilopoietin; D010100:Oxygen