Tumour necrosis factor may contribute to the anaemia of malaria by causing dyserythropoiesis and erythrophagocytosis

Abstract

Among the unexplained changes caused by malaria in several host species, including man and mouse, are erythrophagocytosis and dyserythropoiesis. In order to see whether tumour necrosis factor (TNF) could contribute to these changes we injected recombinant human TNF intravenously into mice made very susceptible to this monokine by low density infection with a mouse malaria (Plasmodium vinckei) or prior injection of an extract of Coxiella burneti. Appreciable erythrophagocytosis, involving nucleated erythroblasts as well as mature red cells, was observed in bone marrow preparations from TNF-treated mice and those with severe illness due to P. vinckei, but in no other group. Dyserythropoiesis, involving irregularly-shaped nuclei and karyorrhexis, had the same distribution. TNF at concentrations up to 8 ng/ml was detected in the serum of all mice with severe malaria, but not uninfected animals or those with light infections. These findings are consistent with TNF making an important contribution to erythrophagocytosis and dyserythropoiesis, and thus to anaemia, in malaria and other conditions.