Reduce Spleen-IFN-γ Correlated with CXCL9 Levels During Cerebral Malaria Phase in Annona muricata-Treated Swiss Mouse Study

Background: Cerebral malaria (CM) cause malaria mortality. Anti-plasmodial and immunomodulatory properties of A. muricata-leaf extract (AME) may provide benefices for CM-patients. IFN-γ, a pivotal cytokine in the CM-immunopathology, is modulated by CXCL9, IL-10 and IL-12. The study objective was to determine factors correlated with spleen-IFN-γ production in health and CM phase with/without ethanolic AME treatment. Method: A post test only controls group design study using 36 Swiss mice randomly divided into 6 groups was performed. The Plasmodium berghei ANKA (PbA)-inoculated and healthy mice were grouped in C(+) and C(−). The healthy mice treated with AME 100 and 150 mg/Kg BW/day were grouped in X ₁ and X ₂. The PbA-inoculated and received either AME dose was grouped in X ₃ and X ₄. Phytohemagglutinin (PHA) induced spleenocyte IFN-γ production, while lipopolysaccharide (LPS) induced IL-10, IL-12 and CXCL9. Elisa was used to measure the observed cytokine production. One-way ANOVA and post hoc test were applied in normally distributed data; otherwise, Kruskal-Wallis and Mann-Whitney test were used. Results: IFN-γ was significantly lower in C(+), X ₃ and X ₄ than C(−) group, and this was also observed in CXCL9. IL-10 was significantly higher in X ₃ and X ₄ than C(+) group (p = 0.003 and p = 0.004). IL-12 was not different among all six groups (p = 0.071). Spearman correlation test showed a correlation between IFN-γ and CXCL9 produced during CM-phase regardless AME treatment (r = 0.581; p = 0.009), while IFN-γ was correlated with IL-10 levels in healthy groups with/without AME treatment (r = 0.544; p = 0.029). Conclusion: The reduce spleen-IFN-γ production might regulate differently in health and CM phase.