The heat shock response, also frequently referred to as the stress response, is an ancient, highly conserved, endogenous cellular defense mechanism characterized by the rapid upregulation of a specific class of
proteins known collectively as
heat shock proteins, or
stress proteins. The 70 kDa family of
heat shock proteins are highly inducible and have been shown to possess important immunomodulatory effects in both the intracellular and extracellular compartments. In the current prospective translational study, we measured extracellular (i.e. plasma) levels of
heat shock protein 72 (Hsp72) in 49 children undergoing
cardiopulmonary bypass (CPB) for either palliation or repair of
congenital heart disease. There was a significant and transient increase (less than 24 h) in extracellular Hsp72 levels following CPB. Extracellular Hsp72 levels significantly correlated with levels of the pro-inflammatory
cytokines interleukin (IL)-6 and
IL-8, as well as the anti-inflammatory
cytokine,
IL-10. In addition, plasma Hsp72 levels correlated with
troponin-I levels, a marker of myocardial injury. Increased extracellular Hsp72 levels at 6 h following CPB were independently associated with increased
length of stay in the cardiac intensive care unit. Importantly, the source of extracellular Hsp72 does not appear to be cardiomyocytes. However, the mechanism of release and clinical relevance of the increase in extracellular Hsp72 need to be further delineated.