TNF-alpha mediates the development of anaemia in a murine Trypanosoma brucei rhodesiense infection, but not the anaemia associated with a murine Trypanosoma congolense infection

Abstract

Development of anaemia in inflammatory diseases is cytokine-mediated. Specifically, the levels of tumour necrosis factor-alpha (TNF-alpha), produced by activated macrophages, are correlated with severity of disease and anaemia in infections and chronic disease. In African trypanosomiasis, anaemia develops very early in infection around the time when parasites become detectable in the blood. Since the anaemia persists after the first waves of parasitaemia when low numbers of trypanosomes are circulating in the blood, it is generally assumed that anaemia is not directly induced by a parasite factor, but might be cytokine-mediated, as in other cases of anaemia accompanying inflammation. To clarify the role of TNF-alpha in the development of anaemia, blood parameters of wild type (TNF-alpha+/+), TNF-alpha-null (TNF-alpha-/-) and TNF-alpha-hemizygous (TNF-alpha-/+) trypanotolerant mice were compared during infections with the cattle parasite Trypanosoma congolense. No differences in PCV, erythrocyte numbers or haemoglobin were observed between TNF-alpha-deficient and wild type mice, suggesting that the decrease in erythrocytes was not mediated by TNF-alpha. Erythropoetin (EPO) levels increased during infection and no significant differences in EPO levels were observed between the three mouse strains. In contrast, during an infection with the human pathogen Trypanosoma brucei rhodesiense, the number of red blood cells in TNF-alpha-deficient mice remained significantly higher than in the wild type mice. These data suggest that more than one mechanism promotes the development of anaemia associated with trypanosomiasis.

Fig. 1

Comparison of PCV from wild type (•), homozygous TNF-α-deficient (○) and hemizygous (+) C57BL/6 mice (a) infected with T. congolense or (b) uninfected. (c) Titres of erythropoietin of infected mice.

Fig. 2

Comparison of relative haemoglobin titres (a) and erythrocyte counts (b) from wild type (•) and TNF-α-knock-out (○) C57BL/6 mice infected with T. congolense (——) or uninfected (- - - -). There were no significant differences (P > 0·05) between parameters of wild type and TNF-α-knock-out mice at any time point.

Fig. 3

Mean red blood cell (RBC) counts and standard deviations from wild type (•) and TNF-α-knock-out (○) C57BL/6 mice, either trypanosome-infected (——) or not (- - - -). (a) T. congolense (infected n = 8, uninfected n = 1). (b) T. brucei rhodesiense (infected n = 10, uninfected n = 4). Significant differences between infected wild type and TNF-α-knock-out mice are indicated by *P < 0·05 or **P < 0·01.