Cytokine dysregulation associated with malarial anemia in Plasmodium yoelii infected mice

Am J Transl Res. 2013;5(2):235-45. Epub 2013 Mar 28.

Abstract

The mechanisms of malaria anemia remain incompletely understood although much effort has been put on studies in both human and murine systems. Hematopoiesis is regulated by the proliferation, differentiation and maturation of erythropoietic progenitor cells into erythrocytes and is tightly controlled by a complex communication network of cytokines as signal mediators. The present study used the murine P. yoelii 17XNL malaria model to investigate the profile of cytokines and leukocytes throughout the entire infection. Moreover, malaria induced anemia was studied in comparison with anemia induced by hemorrhage and hemolysis. During the P. yoelii infection, the levels of erythropoietic-related cytokines, such as G-CSF, GMCSF, IL-7, and IL-17, were pronouncedly reduced, while those of regulatory cytokines, such as IL-10 and TNF-α, were constantly increased. This cytokine profile corresponded well with the cellular composition during the infection, such as drastically decreased levels of CD4(+) and CD8(+) T cells. The cytokine profile during malarial anemia showed the same characteristics as anemia induced by hemorrhage or hemolysis. This study demonstrates that a markedly dysregulated cytokine network occurred in this murine malaria model, which may open a new window of insight into the mechanisms of malaria related anemia.

Keywords: Epo; IL-17; IL-7; Malaria; Plasmodium yoelii; anemia; cytokine; hematopoiesis.