Elevated IL-12, TNF-α, and TNF-α/IL-10 Ratios in Stored Plasmodium falciparum-Infected Whole Blood: Implications for Safe Haemotransfusion

Abstract

Although Plasmodium falciparum infections in blood donors have been reported, the impact of parasitaemia on cytokine levels in stored whole blood has not been explored. This study evaluated the effect of P. falciparum parasitaemia on circulating cytokines and their relationship with haematological parameters in banked blood. In this case-control study, two groups of donor whole blood were recruited: P. falciparum-infected donors (parasitaemia: 515–1877 parasites/μL) and noninfected blood donors (control). At day 0 (baseline), 7, 14, 21, and 35 of banking circulating cytokine levels of tumor necrosis factor alpha (TNF-α), interleukin- (IL-) 12, IL-10, and IL-6 levels and haematological parameters were determined. Kruskal-Wallis test determined differences in weekly cytokine levels while Dunn’s post hoc test determined exact significant points. At baseline, the mean TNF-α (33.81 pg/mL vs. 22.70 pg/mL), IL-12 (28.39 pg/mL vs. 16.15 pg/mL), IL-10 (51.04 pg/mL vs. 18.95 pg/mL), and IL-6 (71.03 pg/mL vs. 30.89 pg/mL) levels were significantly higher in infected donor whole blood. Significant rate of increase was observed in TNF-α, IL-12 levels, and TNF-α/IL-10 ratios in infected blood, while decreased levels were observed in IL-10. IL-6 peaked at day 21 and fell below baseline level at day 35. Significant changes in TNF-α, IL-12, IL-10, IL-6 levels, and TNF-α/IL- 10 ratios in infected donor blood were observed 7 days after storage. Unlike in noninfected stored whole blood, TNF-α, IL-6, IL- 12, and TNF-α/IL-10 ratio levels in infected stored whole blood related inversely to haematological parameters (white cells, red cells, platelets, and haemoglobin levels) during storage. However, in both groups, significant direct relationship was observed in IL-10 and haematological parameters. In conclusion, banking of P. falciparum-infected donor whole blood may lead to infusion of large quantities of inflammatory cytokines with potential adverse immunological response in recipients.