Synthesis and release of interleukin 1 by reoxygenated human mononuclear phagocytes.

作者：Shiro Koga, Satoshi Ogawa, Kosuke Kuwabara, Jerold Brett, J A Leavy, Jane Ryan, Yasuhiro Koga, J M Plocinski, William R. Benjamin, Daniel K. Burns · 发表于：Journal of Clinical Investigation · 年份：1992 · DOI：10.1172/jci115913 · 被引用次数：87 · 研究领域：Immune Response and Inflammation、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、S100 Proteins and Annexins

To examine the possible involvement of cytokines in reperfusion injury, we have studied production of IL-1 by human vascular cells, including smooth muscle and mononuclear phagocytes. Exposure of cells to hypoxia (pO2 approximately 14 torr) followed by reoxygenation led to significant release of IL-1 only from the mononuclear phagocytes. Elaboration of IL-1 was dependent on the oxygen tension and duration of hypoxia (optimal at lower pO2s, approximately 14-20 torr, and after 9 h), as well as the time in reoxygenation (maximal IL-1 release at 6-9 h). Although a period of hypoxia was necessary for subsequent IL-1 production during reoxygenation of either peripheral blood monocytes or cultured monocyte-derived macrophages, no IL-1 release occurred during the hypoxic exposure. IL-1 released during reoxygenation was newly synthesized, and its production was triggered by the generation of oxygen free radicals, as it could be blocked by the addition of either allopurinol or free radical scavengers to cultures and could be stimulated in part by low concentrations of hydrogen peroxide or xanthine/xanthine oxidase. The potential pathophysiological effects of IL-1-containing supernatants from reoxygenated macrophages was shown by their induction of endothelial tissue factor and enhancement of endothelial adhesiveness for neutrophils, both of which could be blocked by anti-IL-1 antibody. The relevance of IL-1 to hypoxia/reoxygenation in vivo was suggested by the presence of circulating n...