Effect of Glutamine on HSP-70 Expression in ICU patients

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DESCRIPTION (provided by applicant): It is well known that enhanced heat shock protein-70 (HSP-70) expression can protect cells and tissues from injury. Further, HSP-70 expression can improve survival in experimental models of critical illness. However, clinical application of these findings has not occurred, as known enhancers of HSP-70 are not safe for human administration. Thus, this very powerful tool, that could possibly significantly improve outcome in critically ill patients, has yet to be clinically applied. Our laboratory has shown that the amino acid glutamine (GLN) can enhance HSP-70 expression in tissues of stressed animals. This expression is correlated with improved survival following experimental models of critical illness. In a small initial trial of critically ill patients we demonstrated GLN could enhance serum HSP-70 levels after one-week of therapy. The effect of GLN on tissue HSP-70 expression and its potential to improve outcomes in patients is unknown. We propose three Specific Aims. The first examines GLN's effect on serum and cellular HSP-70 expression in healthy volunteers following a heat stress. This trial will assess if HSP-70 can be pre-induced to improve outcomes prior to a stressful event, such as surgery. The second Specific Aim will be to assess GLN's effect on serum and cellular HSP-70 expression in critical illness. The third Specific Aim will examine the effect of potentially enhanced HSP-70 expression on clinical outcomes. We believe this study will demonstrate that GLN is the first clinically viable enhancer of HSP-70 expression. The potential for such an agent to reduce morbidity/mortality in surgical and critical illness is significant.