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AcSDKP is down-regulated in anaemia induced by Trypanosoma brucei infection in mice
Musaya, Janelisa; Matovu, Enock; Senga, Edward; Nyirenda, Moffat & Chisi, John
Abstract
Background: Anaemia commonly results from destruction of erythrocytes in the peripheral blood and failure of the bone marrow haematopoietic
cells to replenish the erythrocytes. The mechanisms involved in trypanosoma-induced anaemia, including the role of the bone
marrow haematopoietic cells are incompletely understood. We studied the responses of a tetrapeptide, AcSDKP, and IL-10, and their
association with bone marrow nucleated cells in a Trypanosoma brucei brucei GVR35 experimental infection model.
Methods: Mouse infection was done intraperitoneally with 1 × 103 trypanosomes/mL. Mice were either infected or left uninfected (N = 100).
At days 0, 9, 16, 23, 30, 37, and 44 post-infection, mice were euthanised and blood was collected by cardiac puncture to examine for
parasitaemia and packed cell volume (PCV) and then centrifuged for plasma, which was used for cytokine ELISA. The mice’s femurs
were also dissected and bone marrow was collected for femur cellularity.
Results: PCV dropped from 39.6% to 27% in infected animals by day 9 and remained low (relative to uninfected mice) for the duration of
the experiment. AcSDKP levels decreased from day 0 (11.5 × 104 pg/mL) to day 16 (10 × 104), and increased by day 30 (12.6 × 104).
There was a significant difference at day 16 (P = 0.023) between the infected and uninfected groups. By contrast, expression of IL-10
markedly increased between day 0 (18.6 pg/mL) and day 16 (145 pg/mL) and decreased by day 30 (42.8 pg/mL). There was also a
significant difference in IL-10 expression between infected and uninfected mice at day 16 (P < 0.001). Bone marrow nucleated cells
were significantly reduced during periods of low plasma AcSDKP and high plasma IL-10 concentrations (5.4 × 106 infected vs 6.2 ×
106 on day 0 and 4.9 × 106 infected vs 10 × 106 uninfected on day 16).
Conclusions: These data unravel a possible negative feedback interaction between AcSDKP and IL-10 in trypanosome infection. More importantly,
this study implicates an IL-10/AcSDKP cytokine network in the regulation of bone marrow nucleated cells and provides a new
potential mechanism in the pathogenesis of trypanosoma-induced anaemia. Further mechanistic blocking experiments on AcSDKP
and IL-10 are recommended to further clarify understanding of the interaction.
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