Malaria in Pregnancy Induces a Pro-inflammatory Cytokine Milieu: Comparative Analysis with Non-infected Pregnant and Non-pregnant Women
Emmanuel Ifeanyi Obeagu
*
Division of Haematology, Department of Biomedical and Laboratory Science, Africa University, Zimbabwe and Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Okwudili B. Nwankwo
Department of Haematology, Chukwuemeka Odumegwu Ojukwu University, Awka, Anambra State, Nigeria.
*Author to whom correspondence should be addressed.
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.
Keywords: Malaria in pregnancy, cytokines, TNF, IL-6, IL-10, pregnant women, immune dysregulation