Dyserythropoiesis and severe anaemia associated with malaria correlate with deficient interleukin-12 production.
Complex cytokine interactions occur during blood-stage malaria which offer a unique opportunity to study their influence on the pathogenesis of malarial anaemia. Plasmodium chabaudi AS susceptible A/J mice experience severe and fatal anaemia whereas resistant C57BL/6 (B6) mice survive following moderate anaemia. In this study we analysed the role of IL-12 in erythropoiesis and tested whether the levels of IL-12 produced in these mice correlated with the extent of anaemia. In vitro, IL-12 significantly enhanced the numbers of erythroid burst (BFU-E) and colony forming units (CFU-E) in bone marrow and spleen cells from normal and day 7 infected A/J and B6 mice. Despite the presence of IL-12 in vitro, the level of splenic erythropoiesis in infected A/J mice was significantly lower than in B6 mice. Moreover, sera from infected B6 mice, but not A/J mice, significantly up-regulated erythropoiesis in vitro and this enhancement correlated with several fold higher levels of IL-12 in the sera of B6 compared to A/J mice. Furthermore, the erythropoietic potentiating effect of sera from infected B6 mice was abrogated following depletion of IL-12. Taken together, these findings suggest that defective IL-12 production in A/J mice during the early course of infection may result in fatal anaemia.
Mohan
K
K
McGill Centre for Study of Host Resistance, Montreal General Hospital Research Institute, Quebec, Canada.
Stevenson
M M
MM
D000740:Anemia / Q000097:blood* / Q000473:pathology; D000818:Animals; D002455:Cell Division; D015672:Erythroid Precursor Cells / Q000473:pathology*; D006410:Hematopoiesis / Q000502:physiology*; D018664:Interleukin-12 / Q000172:deficiency / Q000502:physiology*; D008288:Malaria / Q000097:blood*; D051379:Mice; D016788:Plasmodium chabaudi
D018664:Interleukin-12