Th154 - Ontogeny of Plasma Cytokine and Chemokine Concentrations Across the First Four Months of Human Life in a Papua New Guinea Cohort

Abstract Text: Dynamic changes in plasma immune biomarkers in early life follow a robust ontogeny as infants adapt to their new environment. We previously reported that immunomodulatory plasma cytokines and chemokines demonstrate dynamic ontogenetic patterns across the first week of life in neonates from The Gambia. However, whether these changes are generalizable to other regions of the world remains unknown. Here, we examined plasma cytokine and chemokine in Papua New Guinea healthy infants (n=87) across the first four months of life. Using a multiplex assay, 48 cytokines and chemokines concentrations were measured in heparinized peripheral blood plasma samples collected at day of life (DOL) 0, 7, 30, and 128. Unsupervised clustering was used to identify ontogeny patterns in early life. In this cohort, several cytokines and chemokines that shape cellular immunity increased in concentration over the first four months of life, including CXCL10, IFNγ, and IL-2. Contrastingly, other cytokines and chemokines showed reductions, including CXCL8, IL-6, and TGFα. These findings did not appear to be affected by birth season, gestational age, sex, or maternal age. These results validate previously observed patterns in The Gambia, suggesting a universal baseline of cytokine and chemokine trajectories in early life, and illustrating a key role of human immune ontogeny. Understanding early life trajectories of plasma cytokines and highlighting conserved patterns among different geographic populations likely indicates important pathways for human immune development. This may inform novel approaches to diagnosis, treatment, and disease prognosis. Future studies should investigate which cytokines and chemokines deviate in different disease states.