Gerdie M de Jong1, Matthew B B McCall2, Willem A Dik3, Rolf T Urbanus4, Linda J Wammes1, Rob Koelewijn1, Robert W Sauerwein5, Annelies Verbon1, Jaap J van Hellemond1, Perry J J van Genderen6. 1. Department of Medical Microbiology & Infectious Diseases, Erasmus MC University Medical Center, Rotterdam 3015 GD, the Netherlands. 2. Department of Medical Microbiology & Infectious Diseases, Erasmus MC University Medical Center, Rotterdam 3015 GD, the Netherlands; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen 6500HB, the Netherlands. 3. Department of Immunology, Laboratory Medical Immunology, Erasmus MC University Medical Center, Rotterdam 3015GD, the Netherlands. 4. Department of Clinical Chemistry and Haematology, 3584 CX, University Medical Center, Utrecht, the Netherlands. 5. Department of Medical Microbiology, Radboud University Medical Center, Nijmegen 6500HB, the Netherlands. 6. Department of Medical Microbiology & Infectious Diseases, Erasmus MC University Medical Center, Rotterdam 3015 GD, the Netherlands. Electronic address: pjjvangenderen@travelclinic.com.
Abstract
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.
BACKGROUND: After a controlled humanmalaria 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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