Background: After a controlled human malaria infection (CHMI), presentation of clinical signs and symptoms and host responses is heterogeneous. Transforming growth factor-beta (TGF-β) is the first serum cytokine that changes in malaria-naïve volunteers after CHMI. We studied a possible relation between TGF-β changes, pro-inflammatory cytokines, activation of haemostasis and endothelial cells and clinical symptoms. Methods: A panel of cytokines including TGF-β, and markers of activation of haemostasis and endothelial cells were measured in blood samples of 15 volunteers at baseline before CHMI and during CHMI at day of treatment. The change of the parameters on the day of treatment was examined for a significant alteration during infection. Results: Nine of 15 volunteers showed a significant decrease in TGF-β compared to baseline, with concomitant increased concentrations of D-dimer (p = 0.012), Von Willebrand factor (p = 0.017), IL-6 (p = 0.012) and IFN-γ (0.028) and a significantly decreased platelet count (p = 0.011). In contrast, 6 of 15 volunteers showed sustained or increased TGF-β concentrations without change in the aforementioned parameters. The sustained responders presented with less moderate and severe clinical symptoms than the negative responders (p = 0.036) and had a higher baseline lymphocyte count (p = 0.026). TGF-β concentrations did not correlate with the parasitaemia on day of treatment. Conclusion: Early decreases of serum TGF-β might function a marker for a pro-inflammatory host response and downstream clinical symptoms and pathology during CHMI.

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Keywords Clinical symptoms, Controlled human malaria infection, Haemostasis, Heterogeneity, TGF-β
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Journal Cytokine
de Jong, G.M. (Gerdie M.), McCall, M.A, Dik, W.A, Urbanus, R.T, Wammes, L.J, Koelewijn, R, … van Genderen, P.J.J. (2020). Transforming growth factor-beta profiles correlate with clinical symptoms and parameters of haemostasis and inflammation in a controlled human malaria infection. Cytokine, 125. doi:10.1016/j.cyto.2019.154838