Background: The characterization of physiological immune signatures in a population-based cohort enables the identification of pathological immune signatures associated with inflammatory or autoimmune diseases.

Methods: A total of 47 plasma cytokines, chemokines, and growth factors were quantified in 1175 individuals of the SHIP-TREND-0 cohort (532 men and 643 women, aged 20 to 81 years, with a BMI of 17.7 to 53.6) using a bead-based multiplex assay (Merck Milliplex HCYTA-60K) on the FlexMap3D instrument. The relationships between cytokine concentrations and age, sex, body mass index (BMI), season, and blood cell parameters (BCP) were investigated using multivariate regression models.

Results: Higher levels of pro-inflammatory cytokines and chemokines, including IL-6, IL-8, CXCL9, CXCL10, IL-12p40, CCL2, CCL4, CCL11, IL-27, and FLT3LG, were significantly associated with increasing age. Significant sex differences were observed for IL-18, CCL2, CCL4, CCL11, CCL22, CCL3, IL-27, IL-12p40, IL1RA, and TNFα levels. IL-6, IL12p40, and IL-27 levels were affected by BCP. Furthermore, seven cytokines and chemokines, namely CCL4, CCL22, CXCL10, IL-6, IL1RA, IL-18, and TNFα, exhibited elevated levels with increasing BMI. Conversely, only CCL11 demonstrated lower levels with increasing BMI. Additionally, the levels of CCL4, CCL22, CXCL10, IL-6, IL1RA, and CCL11 were found to be significantly distinct between subjects categorised as normal and obese. No significant non-linear seasonal effects were observed for the cytokines under investigation.

Conclusion: This study provides an overview of the circulating cytokines and chemokines and their associations with common phenotypes in the population-based cohort SHIP-TREND-0. This could help to identify the onset of pathological changes as a basis for subsequent studies on common diseases. Furthermore, blood cell parameters should be considered as potential confounders in association studies based on plasma cytokine levels.