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Biomed Res Int. 2014;2014:101023. doi: 10.1155/2014/101023. Epub 2014 Jan 12.

Heat shock protein 72 expressing stress in sepsis: unbridgeable gap between animal and human studies--a hypothetical "comparative" study.

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Pediatric Intensive Care Unit, University Hospital, School of Health Sciences, University of Crete, Voutes Area, 71110 Heraklion, Crete, Greece.
1st Department of Propaedeutic Internal Medicine, Laiko, University General Hospital, University of Athens, 17 Agiou Thoma, 115 27 Athens, Greece.
Department of Clinical Chemistry, School of Medicine, University of Crete, Voutes Area, 71110 Heraklion, Crete, Greece.
National and Kapodistrian University of Athens, First Critical Care Department, Evaggelismos Hospital, Ipsilantou 45, 10676, Athens, Greece.


Heat shock protein 72 (Hsp72) exhibits a protective role during times of increased risk of pathogenic challenge and/or tissue damage. The aim of the study was to ascertain Hsp72 protective effect differences between animal and human studies in sepsis using a hypothetical "comparative study" model. Forty-one in vivo (56.1%), in vitro (17.1%), or combined (26.8%) animal and 14 in vivo (2) or in vitro (12) human Hsp72 studies (P < 0.0001) were enrolled in the analysis. Of the 14 human studies, 50% showed a protective Hsp72 effect compared to 95.8% protection shown in septic animal studies (P < 0.0001). Only human studies reported Hsp72-associated mortality (21.4%) or infection (7.1%) or reported results (14.3%) to be nonprotective (P < 0.001). In animal models, any Hsp72 induction method tried increased intracellular Hsp72 (100%), compared to 57.1% of human studies (P < 0.02), reduced proinflammatory cytokines (28/29), and enhanced survival (18/18). Animal studies show a clear Hsp72 protective effect in sepsis. Human studies are inconclusive, showing either protection or a possible relation to mortality and infections. This might be due to the fact that using evermore purified target cell populations in animal models, a lot of clinical information regarding the net response that occurs in sepsis is missing.

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