Age-dependent differences in the association between blood interleukin-6 levels and mortality in patients with sepsis: a retrospective observational study

Background: Interleukin-6 (IL-6) is a cytokine that predicts clinical outcomes in critically ill patients, including those with sepsis. Elderly patients have blunted and easily dysregulated host responses to infection, which may influence IL-6 kinetics and alter the association between IL-6 levels and clinical outcomes.

Methods: This retrospective observational study included patients aged ≥ 16 years who were admitted to the intensive care unit at Chiba University Hospital. The patients were categorized into two groups: non-elderly (< 70 years) and elderly (≥ 70 years). Associations between log-transformed blood IL-6 levels and 28-day in-hospital mortality (primary outcome) and multiple organ dysfunction (MOD) on days 3 and 7 (secondary outcomes) were examined.

Results: The non-elderly and elderly groups included 272 and 247 patients, respectively. There were no significant differences in the Sequential Organ Failure Assessment score, components of the APACHE II score (Acute physiology score and Chronic health points), MOD at baseline, or any of the outcome measures between the groups. In the non-elderly group, univariate Cox regression analysis showed a significant association between IL-6 levels and mortality (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.25-2.37, P < 0.001). This association remained significant after adjusting for sex, body mass index, steroid use prior to sepsis onset, and number of chronic organ dysfunctions (HR 1.66, 95% CI 1.20-2.32, P = 0.002). However, no significant association was observed in the elderly group in either the univariate (P = 0.69) or multivariable analyses (P = 0.77). Multivariable logistic regression analysis of MOD on days 3 and 7 revealed significant associations between MOD and IL-6 levels in both groups.

Conclusions: Blood IL-6 levels were significantly associated with mortality in non-elderly patients with sepsis, but not in elderly patients. IL-6 levels were associated with MOD in both groups. Therefore, IL-6 levels should be interpreted with caution when predicting mortality in elderly patients with sepsis.

Trial registration: Not applicable.