Tumor necrosis factor α and the anemia of chronic disease: Effects of chronic exposure to TNF on erythropoiesis in vivo

G. D. Roodman, R. A. Johnson, U. Clibon

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19 Scopus citations

Abstract

The anemia of chronic disease is associated with conditions in which macrophage activation occurs. Activated marrow macrophages suppress erythropoiesis in vitro, and produce tumor necrosis factor (TNF). Therefore, we tested the effects of chronic in vivo exposure to TNF to determine if it were a candidate for a mediator of the anemia of chronic disease. Nude mice were inoculated with CHO cells expressing the human TNF gene, or with control cells containing the transfection vector alone. The TNF mice promptly became reticulocytopenic, and after 3 weeks their corrected reticulocytes were 2.6 ± 7% compared to 7.3 ± 4% in control mice. The hematocrit at 3 weeks was 28.4 ± 1.7% in TNF mice compared to 46 ± 8% in control mice. This anemia was also associated with low serum iron and normal iron stores and increased erythropoietin levels. The TNF mice showed an absolute monocytosis with twice the number of circulating monocytes as control mice. The TNF mice also became mildly thrombocytopenic. Marrow CFU-E and BFU-E were profoundly decreased (1.2 ± 2 x 103 vs 8.6 ± 2 x 104 CFU-E per femur, and 6.5 ± 1 x 102 vs 8.5 ± 2 x 104 BFU-E per femur). Splenic CFU-E and BFU-E were similarly depressed. In contrast, marrow CFU-GM and CFU-GEMM were not affected. Administration of recombinant human erythropoietin to these mice failed to reverse the suppressed erythropoiesis in mice bearing TNF producing tumors. These data demonstrated that TNF preferentially inhibits erythropoiesis in vivo, and may be important in the pathogenesis of the anemia of chronic diseases.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
Pages185-196
Number of pages12
Volume271
StatePublished - Oct 2 1990

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Roodman, G. D., Johnson, R. A., & Clibon, U. (1990). Tumor necrosis factor α and the anemia of chronic disease: Effects of chronic exposure to TNF on erythropoiesis in vivo. In Advances in Experimental Medicine and Biology (Vol. 271, pp. 185-196)