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 malari al anaemia. Plasmodium chabaudi AS susceptible A/J mice experience severe a nd fatal anaemia whereas resistant C57BL/6 (B6) mice survive following mode rate 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 w ith the extent of anaemia. In vitro, IL-12 significantly enhanced the numbe rs of erythroid burst (BFU-E) and colony forming units (CFU-E) in bone marr ow 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 inf ected A/J mice was significantly lower than in B6 mice. Moreover, sera from infected B6 mice, but not A/J mice, significantly up-regulated erythropoie sis in vitro and this enhancement correlated with several fold higher level s of IL-12 in the sera of B6 compared to A/J mice. Furthermore, the erythro poietic potentiating effect of sera from infected B6 mice was abrogated fol lowing depletion of IL-12. Taken together, these findings suggest that defe ctive IL-12 production in A/J mice during the early course of infection may result in fatal anaemia.