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Influence of Biological Sex and Congenital Iron Deficiency on Neonatal Cytokine Responses
Narmin Mukhtarova1,2, Anthony Babu2, Christopher L Coe3
1Department of Pediatrics, University of Wisconsin Hospitals and Clinics, Madison, WI 53792, USA.
Insights
Congenital iron deficiency in newborns alters immune cell cytokine responses, with notable sex-specific differences observed. These findings suggest iron status and sex may impact a child's immune development and risk of atopic diseases.
Area of Science:
- Immunology
- Neonatal Health
- Atopic Disease Research
Background:
- Previous research linked stimulated cord blood mononuclear cell (CBMC) cytokine responses to childhood atopic disease risk.
- Iron deficiency (ID) at birth is a potential programming factor for atopic disease.
- Males have a higher risk of pediatric atopic disease, but the impact of congenital ID on immune responses by sex is unknown.
Purpose of the Study:
- To investigate whether congenital iron deficiency differentially impacts CBMC immune responses in male and female neonates.
- To explore the relationship between congenital iron status and cytokine production in cord blood.
Main Methods:
- Cord blood (CB) samples were collected from healthy neonates born via elective cesarean delivery.
- Congenital ID was defined by a transferrin saturation ≤ 25%.
- CBMCs were stimulated with phytohemagglutinin (PHA) alone or with an iron chelator.
Main Results:
- Neonates with congenital ID showed lower plasma TNF-α and higher CBMC TNF-α and IL-8 responses compared to iron-sufficient neonates.
- Congenital ID affected CBMC TNF-α responses similarly in both sexes.
- Females with congenital ID exhibited distinct patterns, including lower plasma IL-6, lower plasma TNF-α, and higher CBMC IL-8.
Conclusions:
- Congenital ID influences stimulated CBMC cytokine responses, indicating sex-specific immune regulation at birth.
- Further research is needed to understand how fetal sex and congenital iron status affect childhood immune responses to infections and environmental antigens.
- Findings highlight the potential role of early-life iron status and sex in immune programming relevant to asthma and other atopic conditions.
Background/Objectives:
Stimulated cord blood mononuclear cell (CBMC) cytokine responses were previously shown to predict the risk of childhood atopic disease. Iron deficiency (ID) at birth may also program atopic disease. Males are at a higher risk of pediatric atopic disease, but it is not known whether congenital ID impacts CBMC immune responses differentially by sex.
Methods:
Cord blood (CB) samples were collected from healthy term or near-term neonates after elective cesarean deliveries. A transferrin saturation ≤ 25% defined congenital ID. CBMCs were stimulated with either phytohemagglutinin (PHA) or PHA plus an iron chelator.
Results:
Of the 85 neonates, the 26 neonates with congenital ID exhibited lower plasma tumor necrosis factor-α (TNF-α), as well as higher CBMC TNF-α and IL-8 responses than iron-sufficient neonates (p = 0.017, p = 0.013, and p = 0.007, respectively). Higher CBMC TNF-α responses were seen in both males and females with congenital ID. However, females with congenital ID also had lower plasma IL-6, lower plasma TNF-α, and higher CBMC interleukin (IL)-8 responses. Additionally, iron chelation during culture influenced stimulated CBMC IFN-γ and CBMC TNF-α responses.
Discussion:
Congenital ID may influence stimulated CBMC cytokine responses, but results point to a sex-specific regulation of immune balance at birth. Because males are more prone to infantile ID and more likely to develop early childhood asthma, future studies should further investigate how fetal sex and congenital iron status impacts childhood immune responsiveness to infections and antigenic stimulation from the rearing environment.
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