Parenteral glutamine increases serum heat shock protein 70 in critically ill patients

Department of Medicine/Center for Clinical and Molecular Nutrition, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Intensive Care Medicine (Impact Factor: 7.21). 09/2005; 31(8):1079-86. DOI: 10.1007/s00134-005-2690-5
Source: PubMed


Heat shock protein 70 (HSP-70) is protective against cellular and tissue injury. Increased serum HSP-70 levels are associated with decreased mortality in trauma patients. Glutamine (Gln) administration increases serum and tissue HSP-70 expression in experimental models of sepsis. Gln has been safely administered to critically ill patients and can improve clinical outcomes, but the effect of Gln administration on HSP-70 expression in humans is unknown. We examined whether Gln-supplemented parenteral nutrition (PN) increases serum HSP-70 levels in critically ill patients.
Randomized, controlled, double-blind study in surgical intensive care units (SICU) in a university hospital.
29 patients admitted to the SICU and requiring PN for more than 7 days.
Patients received either Gln-PN (containing alanyl-glutamine dipeptide; 0.5 g/kg per day; n=15) or standard Gln-free PN (control-PN) that was iso-nitrogenous to Gln-PN (n=14). Serum HSP-70 concentrations were measured at enrollment and at 7 days. Clinical outcome measures were also determined.
HSP-70 concentrations were unchanged in control-PN subjects from baseline to day 7. In marked contrast, Gln-PN subjects demonstrated significantly higher (3.7-fold) serum HSP-70 concentrations than control subjects. In Gln-PN patients there was a significant correlation between increases in HSP-70 levels over baseline and decrease in ICU length of stay.
Gln-PN significantly increases serum HSP-70 in critically ill patients. The magnitude of HSP-70 enhancement in Gln-treated patients was correlated with improved clinical outcomes. These data indicate the need for larger, randomized trials of the Gln effect on serum and tissue HSP-70 expression in critical illness and relationship to clinical outcomes.

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    • "We excluded the outlier from all analyses and naturally log-transformed HSP70 raw values to approximate a normal distribution for analyses. Previous authors have recommended naturally log-transforming HSP70 to obtain a more normal distribution for the analysis of positively skewed data (Howell, 2009), and this approach is consistent with that used in previous research with this biomarker (Mandal et al., 2005; Ziegler et al., 2005). Differences among demographic and study variables were analyzed using independent samples t-tests for continuous variables and Pearson w 2 tests for categorical variables. "
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    ABSTRACT: African American (AA) women are nearly twice as likely as non-Hispanic White (NHW) women to develop atherosclerosis associated with cardiovascular disease. Compelling evidence demonstrates that stress-related biomarkers, such as heat shock protein-70 (HSP70), are associated with increased atherosclerosis risk. Yet little is known about how social factors such as perceived discrimination, subjective social status, and socioeconomic status contribute to the levels of these biomarkers in women with atherosclerosis. The aims of this pilot study were to (1) describe perceived everyday discrimination, subjective social status, perceived stress, and HSP70 level in AA and NHW women diagnosed with coronary or carotid artery disease requiring intervention and (2) determine the extent to which perceived discrimination, subjective social status, and perceived stress are associated with HSP70 level, controlling for age, education, and race. The sample for this cross-sectional, descriptive pilot study consisted of 10 AA and 21 NHW women admitted to the hospital for elective percutaneous cardiac intervention or carotid endarterectomy. Participants completed questionnaires measuring psychosocial variables and provided blood samples for analysis of HSP70. Race, age, education, perceived stress, perceived discrimination, and subjective social status significantly (p = .022) explained 34% of the variance in HSP70 levels. However, only subjective social status (p = .031) and AA race (p = .031) were significant independent predictors of HSP70 levels, with lower subjective social status and AA race associated with higher HSP70. Although larger studies are needed to confirm these results, findings imply that race and subjective social status may play an important role in predicting stress biomarker levels.
    Biological Research for Nursing 06/2013; 16(3). DOI:10.1177/1099800413491422 · 1.43 Impact Factor
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    • "In the extracellular milieu, Hsp72 is suggested to improve immune function. For example, it has been shown that the concentration of eHsp70 is highly correlated with oxidative stress, inflammation, cardiovascular, and pulmonary disease (Ogawa et al. 2008), and that the artificial increase in eHsp70 via glutamine supplementation is associated with a reduced hospital treatment period in critically ill patients (Ziegler et al. 2005). As such, an increase in eHsp72 may represent an important immuno-inflammatory response to protect the organism against physiological disturbances (Heck et al. 2011). "
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    ABSTRACT: Extracellular heat-shock protein 72 (eHsp72) expression during exercise-heat stress is suggested to increase with the level of hyperthermia attained, independent of the rate of heat storage. This study examined the influence of exercise at various intensities to elucidate this relationship, and investigated the association between eHsp72 and eHsp27. Sixteen male subjects cycled to exhaustion at 60% and 75% of maximal oxygen uptake in hot conditions (40°C, 50% RH). Core temperature, heart rate, oxidative stress, and blood lactate and glucose levels were measured to determine the predictor variables associated with eHsp expression. At exhaustion, heart rate exceeded 96% of maximum in both conditions. Core temperature reached 39.7°C in the 60% trial (58.9 min) and 39.0°C in the 75% trial (27.2 min) (P < 0.001). The rate of rise in core temperature was 2.1°C h(-1) greater in the 75% trial than in the 60% trial (P < 0.001). A significant increase and correlation was observed between eHsp72 and eHsp27 concentrations at exhaustion (P < 0.005). eHsp72 was highly correlated with the core temperature attained (60% trial) and the rate of increase in core temperature (75% trial; P < 0.05). However, no common predictor variable was associated with the expression of both eHsps. The similarity in expression of eHsp72 and eHsp27 during moderate- and high-intensity exercise may relate to the duration (i.e., core temperature attained) and intensity (i.e., rate of increase in core temperature) of exercise. Thus, the immuno-inflammatory release of eHsp72 and eHsp27 in response to exercise in the heat may be duration and intensity dependent.
    Cell Stress and Chaperones 01/2012; 17(3):375-83. DOI:10.1007/s12192-011-0313-3 · 3.16 Impact Factor
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    • "Heat shock protein plays a role in tissue protection after stress or injury, as its absence leads to an increase in cellular apoptosis. Glutamine induces expression of heat shock protein and reduces expression of inflammatory cytokines.34 The effect of glutamine on the induction of heat shock protein may be related to the beneficial effects of glutamine supplementation, such as a decrease in length of hospital stay and ventilator time in critically ill patients.35 "
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    ABSTRACT: Dietary supplementation with nutrients enhancing immune function is beneficial in patients with surgical and critical illness. Malnutrition and immune dysfunction are common features in hospitalized patients. Specific nutrients with immunological and pharmacological effects, when consumed in amounts above the daily requirement, are referred to as immune-enhancing nutrients or immunonutrients. Supplementation of immunonutrients is important especially for patients with immunodeficiency, virus or overwhelming infections accompanied by a state of malnutrition. Representative immunonutrients are arginine, omega-3 fatty acids, glutamine, nucleotides, beta-carotene, and/or branched-chain amino acids. Glutamine is the most abundant amino acid and performs multiple roles in human body. However, glutamine is depleted from muscle stores during severe metabolic stress including sepsis and major surgery. Therefore it is considered conditionally essential under these conditions. This review discusses the physiological role of glutamine, mode and dose for glutamine administration, as well as improvement of certain disease state after glutamine supplementation. Even though immunonutrition has not been widely assimilated by clinicians other than nutritionists, immunonutrients including glutamine may exert beneficial influence on diverse patient populations.
    Yonsei medical journal 11/2011; 52(6):892-7. DOI:10.3349/ymj.2011.52.6.892 · 1.29 Impact Factor
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