Editorial: Cytokines in inflammation, aging, cancer and obesity

Early life is marked by distinct and rapidly evolving immunity and increased susceptibility to infection. The vulnerability of the newborn reflects development of a complex immune system in the face of rapidly changing demands during the transition to extra-uterine life. Cytokines and chemokines contribute to this dynamic immune signaling network and can be altered by many factors, such as infection. Newborns undergo dynamic changes important to health and disease, yet there is limited information regarding human neonatal plasma cytokine and chemokine concentrations over the first week of life. The few available studies are limited by small sample size, cross-sectional study design, or focus on perturbed host states like severe infection or prematurity. To characterize immune ontogeny among healthy full-term newborns, we assessed plasma cytokine and chemokine concentrations across the first week of life in a robust longitudinal cohort of healthy, full-term African newborns.

We analyzed a subgroup of a cohort of healthy newborns at the Medical Research Council Unit in The Gambia (West Africa; N = 608). Peripheral blood plasma was collected from all study participants at birth (day of life (DOL) 0) and at one follow-up time point at DOL 1, 3, or 7. Plasma cytokine and chemokine concentrations were measured by bead-based cytokine multiplex assay. Unsupervised clustering was used to identify patterns in plasma cytokine and chemokine ontogeny during early life.

We observed an increase across the first week of life in plasma Th1 cytokines such as IFNγ and CXCL10 and a decrease in Th2 and anti-inflammatory cytokines such as IL-6 and IL-10, and chemokines such as CXCL8. In contrast, other cytokines and chemokines (e.g. IL-4 and CCL5, respectively) remained unchanged during the first week of life. This robust ontogenetic pattern did not appear to be affected by gestational age or sex.

Ontogeny is a strong driver of newborn plasma-based levels of cytokines and chemokines throughout the first week of life with a rising IFNγ axis suggesting post-natal upregulation of host defense pathways. Our study will prove useful to the design and interpretation of future studies aimed at understanding the neonatal immune system during health and disease.

The role of the intestinal immune system in the inhibition of fat tissue-related inflammation by dietary material is yet to be elucidated. Oral administration of β-elemene, contained in various foodstuffs, downregulated expressions of inflammatory cytokines and increased Foxp3⁺CD4⁺ T cells in adipose tissue of obese mice. However, β-elemene did not affect the inflammatory response of adipose tissue in vitro, suggesting that the inhibition observed in vivo was not due to direct interactions of adipose tissue with β-elemene. Instead, β-elemene increased Foxp3⁺CD4⁺ T cell population enhancing gene expressions of transforming growth factor β 1, retinaldehyde dehydrogenase 2, integrin αvβ8, and interleukin-10 in intestinal dendritic cells (DCs) in vivo and in vitro. Taken together, this study suggested the therapeutic effects of β-elemene on treating experimental obesity-induced chronic inflammation by adjusting the balance of immune cell populations in fat tissue through the generation of regulatory T cells in the intestinal immune system by modulating DC function.