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

Chronic inflammatory diseases are often associated with decreased red blood cell (RBC) mass. The cytokines cachectin/tumor necrosis factor‐a (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 1α, 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. [ 59 Fe]RBC survival was significantly shortened in animals given cachectin, IL 1 or endotoxin, but the magnitude of the response was greatest in cachcctin/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 59 Fe into newly synthesized RBCs. We conclude that chronic cachectin/TNF administration produces anemia by decreasing RBC synthesis and reducing the life span of circulating RBCs. An endogenous cachectin/TNF response during inflammatory disease may contribute to an associated anemic state, whereas the modestly reduced red cell life span induced by IL 1 does not lead to a net reduction in RBC mass, presumably owing to a preserved RBC synthetic rate.—M oldawer , L. L.; M arano , M. A.; W ei , H.; F ong , Y.; S ilen , M. L.; Kuo, G.; M anogue , K. R.; V lassara , H.; C ohen , H.; C erami , A.; L owry , S. F. Cachectin/tumor necrosis factor‐α alters red blood cell kinetics and induces anemia in vivo. FASEB J. 3: 1637‐1643; 1989.