Cachectin/tumor necrosis factor‐α alters red blood cell kinetics and induces anemia in vivo

作者：Lyle L. Moldawer, Michael A. Marano, Wei He, Yuman Fong, Mark L. Silen, George C. Kuo, Kirk R. Manogue, Helen Vlassara, Harvey J. Cohen, Anthony Cerami, Stephen F. Lowry · 发表于：The FASEB Journal · 年份：1989 · DOI：10.1096/fasebj.3.5.2784116 · 被引用次数：227 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Blood properties and coagulation、Erythrocyte Function and Pathophysiology

Chronic inflammatory diseases are often associated with decreased red blood cell (RBC) mass. The cytokines cachectin/tumor necrosis factor-alpha (TNF) and interleukin 1 (IL 1) are produced by monocytes/macrophages in response to many inflammatory stimuli and have been implicated in the anemia of chronic disease. This study was undertaken to evaluate the mechanisms by which cachectin/TNF, IL 1, or endotoxin induce anemia. Hematologic parameters and RBC kinetics were quantitated in rats given chronic sublethal quantities of either recombinant human cachectin/TNF, recombinant human IL 1 alpha, or Salmonella endotoxin for 7 days. Cachectin/TNF or endotoxin treatment resulted in a 25 or 31% decrease, respectively, in total RBC mass, whereas RBC mass was unchanged by IL 1 administration. Anemia associated with either chronic cachectin or endotoxin administration was characterized by normal mean corpuscular volume, mean corpuscular hemoglobin content, and reticulocyte numbers. [59Fe]RBC survival was significantly shortened in animals given cachectin, IL 1 or endotoxin, but the magnitude of the response was greatest in cachectin/TNF-or endotoxin-treated rats. Although cachectin/TNF-IL 1-, or endotoxin treatment resulted in similar hypoferremia and shortened plasma iron half-life, endotoxin or cachectin/TNF treatment (but not IL 1) significantly reduced the incorporation of plasma 59Fe into newly synthesized RBCs. We conclude that chronic cachectin/TNF administration produces anemia b...