Checkpoint for Considering Interleukin-6 as a Potential Target to Mitigate Secondary Brain Injury after Cardiac Arrest

Abstract

Interleukin-6 (IL-6) was suggested as a potential target for intervention to mitigate brain injury. However, its neuro-protective effect in post-resuscitation care has not been proven. We investigated the time-course of changes in IL-6 and its association with other markers (systemic inflammation and myocardial and neuronal injury), according to the injury severity of the cardiac arrest. This retrospective study analyzed IL-6 and other markers at baseline and 24, 48, and 72 h after the return of spontaneous circulation. The primary outcome was the association of IL-6 with injury severity as assessed using the revised Post-Cardiac Arrest Syndrome for Therapeutic Hypothermia scoring system (low, moderate, and high severity). Of 111 patients, 22 (19.8%), 61 (55.0%), and 28 (25.2%) had low-, moderate-, and high-severity scores, respectively. IL-6 levels were significantly lower in the low-severity group than in the moderate- and high-severity groups at baseline and at 24 h and 72 h (p < 0.005). While IL-6 was not independently associated with neuronal injury markers in the low-severity group, it was demonstrated to be associated with it in the moderate-severity (β [95% CI] = 4.3 [0.1–8.6], R2 = 0.11) and high-severity (β [95% CI] = 7.9 [3.4–12.5], R2 = 0.14) groups. IL-6 exhibits distinct patterns across severity and shows differential associations with systemic inflammation or neuronal injury.