Hepcidin, Iron Restriction and Oxidative Stress in Women with Latent Toxoplasmosis: A Case–Control Study

Abstract

Background: Latent infection with Toxoplasma gondii is among the most widespread chronic parasitic conditions worldwide, yet it is usually regarded as clinically silent. Persistent low-grade immune activation during the latent stage may perturb systemic iron handling through the interleukin-6 (IL-6)–hepcidin axis, with downstream consequences for redox balance. We examined serum hepcidin, iron indices, lipid peroxidation and antioxidant status in women with serologically defined latent toxoplasmosis.

Methods: In this case–control study, 40 women with latent toxoplasmosis (anti-T. gondii IgG positive, IgM negative, high IgG avidity) and 20 seronegative women matched for age and body mass index were recruited at Samarra General Hospital, Salah al-Din, Iraq, between October 2024 and February 2025. Serum hepcidin, ferritin, malondialdehyde (MDA), reduced glutathione (GSH) and IL-6 were measured by enzyme-linked immunosorbent assay, and serum iron colorimetrically. Groups were compared with Welch's t-test and the Mann–Whitney U test; associations were examined by Spearman and partial correlation with false-discovery-rate correction, multivariable linear regression with variance inflation factors, and bootstrap mediation analysis.

Results: Infected women had higher hepcidin (31.48 ± 4.32 vs 21.11 ± 3.29 ng/mL; p < 0.001; d = 2.58), ferritin (113.98 ± 25.57 vs 79.72 ± 16.87 ng/mL; p < 0.001), MDA (324.50 ± 29.49 vs 245.90 ± 23.27 ng/mL; p < 0.001) and IL-6 (6.16 ± 1.15 vs 3.72 ± 0.55 pg/mL; p < 0.001), with lower serum iron (12.01 ± 2.18 vs 15.35 ± 1.70 µmol/L; p < 0.001) and GSH (1.83 ± 0.21 vs 2.24 ± 0.19 µg/mL; p < 0.001). Within cases, hepcidin correlated with IL-6 (ρ = 0.437; q = 0.012), MDA (ρ = 0.561; q = 0.001) and inversely with serum iron (ρ = −0.574; q = 0.001); these associations persisted after adjustment for age, body mass index and ferritin. Mediation analysis indicated that the association between infection and serum iron was largely indirect, operating through IL-6 and hepcidin (serial indirect effect −0.720, 95% CI −1.362 to −0.140), with a non-significant direct path (c′ = 0.233; p = 0.769).

Conclusions: Latent toxoplasmosis in women is associated with a coherent biochemical pattern of hepcidin-associated iron restriction coupled with increased lipid peroxidation and reduced antioxidant capacity. Because transferrin saturation, C-reactive protein and haemoglobin were not available, the presence of true functional iron restriction requires confirmation; nevertheless, these findings argue against the assumption that the latent stage is metabolically inert.