title: Human alveolar macrophages suppress interleukin-1 (IL-1) activity via the secretion of prostaglandin E2.
abstract: It has been suggested that human alveolar macrophages have a limited capacity to release interleukin-1 (IL-1). To determine whether this apparent defect in cell function is related to the release of factors that inhibit the response of lymphocytes to IL-1, we evaluated the capacity of human alveolar macrophages to release prostaglandin E2 (PGE2), a factor that is known to suppress the response of lymphocytes to IL-1. The amount of PGE2 released by alveolar macrophages was dependent on the amount of LPS present in the cultures and the amount of time the cells were present in culture. After 24 h in culture, the alveolar macrophage supernatants contained sufficient amounts of PGE2 to significantly suppress PHA-induced lymphocyte proliferation (p less than 0.01), IL-1-induced thymocyte proliferation (p less than 0.001), but not IL-2-induced lymphocyte proliferation (p greater than 0.2). Consistent with these observations, only small amounts of IL-1 activity could be detected in 24-h supernatants of LPS-stimulated alveolar macrophages using thymocyte proliferation as an assay for IL-1. Using a more sensitive assay for IL-1, however, it was demonstrated that the supernatants of LPS-stimulated macrophages contained amounts of IL-1 that were not significantly different from those present in supernatants of LPS-stimulated monocytes. Indomethacin (1 microgram/ml) completely suppressed the release of PGE2 by alveolar macrophages. These observations suggest that the apparent defect in the release of IL-1 by human alveolar macrophages may be due in part to the release of large amounts of PGE2, which suppresses various lymphocyte functions.
mesh_terms: D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation / Q000379:methods; D015232:Dinoprostone; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011458:Prostaglandins E / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000276:immunology*; D013997:Time Factors
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D011458:Prostaglandins E; C036757:lipopolysaccharide B; D015232:Dinoprostone