Longitudinal dynamics of serum IL-33 and sST2 across age and sex in a healthy Finnish cohort before and after Tdap booster vaccinations.

BACKGROUND: Interleukin-33 (IL-33) and soluble ST2 (sST2) are critical regulators of tissue-derived inflammation, and their dysregulation is usually implicated in various inflammatory disorders. Despite this, how these circulating proteins behave over time in healthy individuals remains poorly defined. Therefore, defining reference concentrations in healthy cohorts is important for interpreting disease-associated changes attributed to these proteins. METHODS: A healthy Finnish cohort (N = 124), consisting of children (7-10y, n = 36), adolescents (11-15y, n = 37), young adults (20-34y, n = 25), and older adults (60-70y, n = 23), received a Tdap3-IPV (aP) booster at day 0. Serum IL-33 and sST2 were measured at baseline (before vaccination) and at days 28 and 365 post-vaccination. For the same time points, serum antibodies specific to aP booster were measured. Baseline serum concentrations of IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-17A and IL-17F were evaluated as predictors of sST2 dynamics. RESULTS: IL-33 was undetectable at a population level (10-30% detectability). In contrast, sST2 was consistently detectable across all time points (median baseline 18.49 ng/mL) but exhibited a significant longitudinal decline over one year (p < 0.001). This longitudinal decline varied by age: older adults showed lower baseline sST2 and minimal change over time, whereas younger age groups showed a more pronounced decline. No associations were observed between IL-33 or sST2 and vaccine responses or baseline cytokines. CONCLUSION: Serum IL-33 was mostly undetectable in healthy individuals. Although serum sST2 concentrations declined over time, these changes were independent of vaccine-induced antibody responses. These results provide reference serum concentrations for the two important proteins.