Association between cytokine network and organ damage in crush syndrome

Abstract

Abstract Crush syndrome, a fatal disease caused by prolonged compression of the extremities, produces lethal arrhythmias and acute renal failure. In crush syndrome, injury-related molecular patterns are released into the blood from the contused tissue, and cytokines are produced by activated immune cells. Excessive cytokine production triggers a systemic inflammatory response. In severe cases, inflammation becomes difficult to control, leading to multiple organ damage. This study evaluated the relationship between cytokine networks and organ damage in crush syndrome. In the established rat crush syndrome model, serum was collected 6 and 24 hours after crush injury, and TNF-α, IL-1β, IL-6, IL-8, and IL-10 were evaluated by ELISA. At both time points, hematoxylin and eosin staining was performed on collected lung tissue, and lung injury was evaluated by Lung Injury Score (LIS). IL-1β, IL-6, IL-8, and IL-10 were elevated at 6 and 24 hours after crush injury. Hierarchical clustering and network analysis confirmed formation of this common cytokine network at each time point. The network including these common cytokines also correlated strongly with LIS at each time point. Collectively, we found a cytokine network including IL-1β, IL-6, IL-8, and IL-10 to be associated with organ damage in the acute phase after crush injury.