Effect of dexamethasone on the myocardial expression of cytokines and heat shock proteins in human neonates

Background and aim

Cardiac surgery with cardiopulmonary bypass (CPB) stimulates the synthesis of the proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), IL-6, IL-8, and anti-inflammatory cytokines such as IL-10. This study was intended to analyze the effect of preoperative administration of dexamethasone on gene expression of proinflammatory and antiinflammatory cytokines and heat shock protein in the myocardium.

Methods

Neonates (n = 22) scheduled for arterial switch operation were double-blinded randomized to receive dexamethasone (n = 11) (1 mg/kg) or saline (n = 11) given intravenously 2 hours before induction of anesthesia. Biopsies were taken from the right atrial appendage immediately before initiation of CPB. Myocardial gene expression and synthesis of TNF-α, IL-1β, IL-6, IL-8, IL-10, and of heat shock proteins HSP32, HSP90, and HSP70 were detected by quantitative real-time RT-PCR and by western blot.

Results

Proinflammatory and anti-inflammatory cytokines as well as HSPs were expressed at the mRNA level. IL-6 and HSP70 were also expressed at the protein level. Expression of mRNA encoding for TNF-α, IL-1β, IL-6, IL-8, IL-10, and HSP32 were lower in neonates treated with dexamethasone than in the others. In contrast, expression of HSP70 mRNA and for HSP90 mRNA and protein levels of IL-6 and HSP70 were not different between both groups.

Conclusion

Our study shows for the first time expression of proinflammatory and antiinflammatory cytokines and of HSPs in the myocardium of human neonates undergoing cardiac surgery. Dexamethasone given before cardiac surgery is associated with a reduction of cytokine expression at induction of CPB. This might provide myocardial protection.