Malaria in Pregnancy Induces a Pro-inflammatory Cytokine Milieu: Comparative Analysis with Non-infected Pregnant and Non-pregnant Women

Abstract

Background: Malaria in pregnancy is associated with adverse maternal and fetal outcomes, partly driven by immune dysregulation and altered cytokine responses. Pro-inflammatory and anti-inflammatory cytokines influence disease severity, yet their precise profiles in malaria-infected pregnant women remain incompletely characterized in malaria-endemic regions. Objective: To compare plasma cytokine levels (TNF, IL-6, IL-10, and IL-4) among malaria-infected pregnant women (MP+), malaria-uninfected pregnant women (MP−), and non-pregnant controls. Methods: This cross-sectional comparative study enrolled 150 participants (50 MP+, 50 MP−, and 50 non-pregnant controls) recruited in Owerri, Nigeria. Malaria infection was confirmed by Giemsa-stained thick and thin blood smear microscopy, with rapid diagnostic tests employed for supplemental confirmation when necessary. Plasma concentrations of TNF, IL-6, IL-10, and IL-4 were measured using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using descriptive statistics, independent-samples t-tests, and one-way analysis of variance (ANOVA) with Tukey post-hoc tests. Results: Malaria-infected pregnant women exhibited significantly higher TNF (13.54 ± 2.05 pg/mL) and IL-6 (25.1 ± 4.9 pg/mL) compared with malaria-uninfected pregnant women (TNF: 11.25 ± 2.10 pg/mL; IL-6: 19.8 ± 2.9 pg/mL; p < 0.001) and non-pregnant controls (TNF: 10.61 ± 1.73 pg/mL; IL-6: 19.9 ± 3.7 pg/mL; p < 0.001). IL-10 was moderately elevated in MP+ women (26.15 ± 4.21 pg/mL) relative to MP− (22.75 ± 11.2 pg/mL; p = 0.023) and controls (23.08 ± 13.5 pg/mL; p = 0.024). IL-4 concentrations did not differ significantly among the groups. ANOVA confirmed significant overall group differences for TNF (F = 28.3, p < 0.001), IL-6 (F = 44.7, p < 0.001), and IL-10 (F = 4.0, p = 0.021), but not IL-4 (F = 0.94, p = 0.39). Conclusion: During pregnancy, malaria infection elicits a predominantly pro-inflammatory cytokine response, marked by increased TNF and IL-6 alongside a compensatory rise in IL-10, while IL-4 levels remain stable. This immune imbalance highlights potential biomarkers for disease severity and identifies TNF, IL-6, and IL-10 as promising targets for therapeutic intervention in malaria-endemic regions.