Abstract

BackgroundCardiac dysfunction is a common complication associated with major burns. While recent findings have linked the Th-17 T-cell response to the development of autoimmune myocarditis, the role of IL-17 and the Th-17 T-cell response in the development of post-burn cardiac dysfunction remains unknown.MethodsMale C57BL/6 mice were subjected to a major burn (3rd degree, 25% TBSA) or sham treatment. Three hours after injury plasma and tissue (i.e., heart, lung, liver, small intestine) samples were collected and analyzed for the expression of Th-17 cytokine (i.e., IL-6, IL-17, IL-22, IL-23, TGF-β) levels by ELISA.ResultsCardiac tissue levels of the Th-17 cytokines, IL-6, IL-17 and IL-22 were significantly elevated at 3 hrs after burn as compared to sham levels. IL-17 was analyzed 1, 3 and 7 days after burn and showed a return to baseline levels and without a difference in the burn group. Burn-induced alterations in the level of these cytokines in plasma or other tissues were not evident. The cardiac Th-17 cytokine response after burn injury was specific, as cardiac levels of Th-1 (IFN-γ) and Th-2 (IL-10) cytokines were not significantly affected after injury. The cardiac Th-17 response correlated with a significant increase in Troponin levels at 3 hr. after burn.ConclusionThese findings indicate that early after burn, cardiac tissue is associated with significantly elevated levels of Th-17 cytokines. The early Th-17 response after burn appears to be specific for cardiac tissue and may promote myocardial inflammation and dysfunction associated with this form of trauma.

Highlights

  • Cardiac dysfunction is a common complication associated with major burns

  • Studies have shown differences in the cytokine expression profile in severely burned patients and in the magnitude of the systemic and compartmental inflammatory response correlated with progressive left ventricular contraction and relaxation defects, achieving a nadir with 40% of total body surface area (TBSA) burn [3,4]

  • Based on the observation that the IL-17 response was significantly higher at 3 hrs after burn, all subsequent analysis was conducted on that group of animals

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Summary

Introduction

Cardiac dysfunction is a common complication associated with major burns. Cardiac dysfunction after burn has been well described and has been shown to play an important role in patient outcome [1]. Excessive production of pro-inflammatory cytokines, interleukin (IL)-6 IL-1b and tumor necrosis factor-a (TNF-a) have been associated with the cardiac cell damage [3]. Studies have shown differences in the cytokine expression profile in severely burned patients and in the magnitude of the systemic and compartmental inflammatory response correlated with progressive left ventricular contraction and relaxation defects, achieving a nadir with 40% of TBSA burn [3,4]. While studies have implicated cardiomyocytes as a cellular source of pro-inflammatory cytokines after burn, other cell populations are clearly important [5,6]

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