Tumor necrosis factor alpha and the anemia associated with murine malaria.
The anemia associated with malaria is complex, and multiple factors contribute to its severity. An increased destruction and a decreased production of erythrocytes are involved; however, the mechanisms responsible remain unclear. Tumor necrosis factor alpha (TNF-alpha), released by macrophages in response to infection, is thought to play a role through its ability to inhibit erythropoiesis. In these studies we have examined erythropoiesis in mice infected with Plasmodium berghei and in mice infused with recombinant TNF-alpha via implanted osmotic pumps. In both groups of mice there was (i) a reduction of pluripotent stem cells in the bone marrow and a concomitant increase in the spleen, (ii) a reduction of erythroid progenitor cells, and (iii) a reduced incorporation of 59Fe into erythrocytes. When P. berghei-infected mice were given antiserum against recombinant murine TNF, erythropoiesis was partially restored. There was a significant increase in bone marrow stem cells, erythroid progenitor cells, and 59Fe incorporation into erythrocytes in P. berghei-infected mice that had been treated with anti-TNF. How TNF may act, directly or indirectly, to inhibit erythropoiesis is not yet clear. These results demonstrate that TNF mediates, in part, the anemia associated with malaria.
Miller
K L
KL
Division of Cell and Molecular Biology, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Silverman
P H
PH
Kullgren
B
B
Mahlmann
L J
LJ
D000818:Animals; D000937:Antigen-Antibody Reactions; D001853:Bone Marrow / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008288:Malaria / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha