Tumor necrosis factor alpha and the anemia associated with murine malaria

Abstract

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-a), 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-a 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.

Acute Plasmodium berghei Mouse Infection Elicits Perturbed Erythropoiesis With Features That Overlap With Anemia of Chronic Disease

“…Indeed, the balance between pro-and antiinflammatory cytokines is likely to be a critical determinant of anemia. Several of these cytokines, such as TNF-α and IFN-γ play a protective role in malaria by arresting parasite replication and enhancing parasite killing (Clark et al, 1990), but also contribute to anemia by inhibiting erythropoiesis (Miller et al, 1989;Dufour et al, 2003).…”

Premature removal of uninfected erythrocytes during malarial infection of normal and immunodeficient mice

“…Abnormalities of bone marrow cellularity are clearly visible in infected patients and are reflected in the circulation by low reticulocyte counts [2]. Similar aberrant cellular events are seen during murine infections, with a depletion of bone marrow stem cells as well as a decline in burst-forming units (BFU-E) [3,4]. However, in the murine model the spleen is the dominant erythropoietic organ, and because it shows a lower degree of dyserythropoiesis [5] it partially compensates for the reduced reticulocytosis from the bone marrow.…”

Tumour necrosis factor production by monocytes from cattle infected with Trypanosoma (Duttonella) vivax and Trypanosoma (Nannomonas) congolense: possible association with severity of anaemia associated with the disease

“…In malaria, the macrophage-derived cytokine tumour necrosis factor (TNF) has been shown to be an important mediator of aneamia. TNF was detected in plasma from infected mice (Clark & Chaudri 1988) and was shown to be responsible for the induction of erythrophagocytosis and dyserythropoiesis during disease (Clark & Chaudri, 1988, Miller et al 1989. There is indirect evidence that TNF might be induced during bovine trypanosomiasis.…”