Document Type


Publication Date



Maine Medical Center, Critical Care Medicine, Medical Education, Maine Medical Center Research Institute, Center for Molecular Medicine, Cardiology

MeSH Headings

interleukin-21, Interleukins, Heart Arrest


Purpose/Background: Patients resuscitated from cardiac arrest (CA) have highly variable neurological, circulatory, and systemic ischemia-reperfusion injuries. The initial ischemic insult triggers immune and inflammatory responses, and results in a cascade of secondary injuries that are often fatal. Previous studies using animal’s model of cardiac arrest/cardiopulmonary resuscitation have demonstrated that interleukin-21 (IL-21) promotes brain injury through stimulation of lymphocytes accumulation. However, the role of IL-21 in neurological injury in humans has not been well characterized. The goal of this project was to determine the level of IL-21 in patients with cardiac arrest and resuscitation.

Methods/Approach: Post-cardiac arrest subjects underwent phlebotomy at 24, 48, and 72 hours after resuscitation. The blood plasma was then analyzed using a enzyme-linked immunosorbent assay (ELISA) to measure the levels of circulating IL-21 in 50 patients with cardiac arrest and resuscitation.Thirty one patients underwent coronary artery bypass grafting (CABG) surgery served as a control group. The level of IL-21 was read using a Biotek Epoch Plate Reader. The values of IL-21 were calculated using standard curve (R&D Systems test kit). The correlation analysis between the level of IL-21 and various clinical parameters, including time to return of spontaneous circulation, survival, and cerebral performance category (CPC) score was performed using Spearman's rank-order correlation.

Results: We found large inter-individual variability in the levels of IL-21 in both control subjects and post-cardiac arrest patients. However, no significant changes were found in the levels of IL-21 between CABG and cardiac arrest. The level of IL-21 remained stable at different time points after cardiac arrest. A positive trend was found between the level of IL-21 at 24 hours post-cardiac arrest and survival at day 7 (p=0.100).

Conclusion: Our study identified significant inter-individual variability in the level of circulating IL-21, signifying the potential involvement of this cytokine into a variety of clinical phenotypes after cardiac arrest. A positive trend between the level of IL-21 and survival may indicate that high level of IL-21 is associated with a better chance to survive after cardiac arrest. However, further studies at early time points e.g., 6 hours or 12 hours post-cardiac arrest, are warranted.


2020 Costas T. Lambrew Research Retreat