ABSTRACT: Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.
*Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center, Vienna, Austria; †Boston University School of Medicine and ‡Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; §Pennsylvania State College of Medicine, Hershey, Pennsylvania; ∥Oslo University Hospital, Oslo, Norway; ¶Ehime University, Matsuyama, Japan; **Research and Education Institute, Hospital Sirio-Libanes, São Paulo, Brazil; ††Institute of Surgical Research, University of Szeged, Szeged, Hungary; ‡‡State University of New York Upstate Medical University, Syracuse, New York; §§Department of Biological and Environmental Sciences, University of Messina, Messina, Italy; ∥∥Southern Medical University Guangzhou, Guangzhou, China; ¶¶Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; ***Chiba University Graduate School of Medicine, Chiba, Japan; †††Washington University School of Medicine, St Louis, Missouri; ‡‡‡University of Kentucky College of Medicine, Lexington, Kentucky; §§§Ulm Medical University Clinic, Ulm, Germany; ∥∥∥Division of Infectious Diseases, Department of Medicine, Hospital São Paulo–Escola Paulista de Medicina, Federal University of São Paulo, Sao Paulo, Brazil; ¶¶¶University of Indonesia, Jakarta, Indonesia;****The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; ††††University of Brussels, Erasme University Hospital, Brussels, Belgium; ‡‡‡‡The University of Michigan Medical School, Ann Arbor, Michigan; §§§§Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China; ∥∥∥∥Chang Gung Memorial Hospital, Taipei, Taiwan; ¶¶¶¶Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; and *****University of Alabama at Birmingham, Birmingham, Alabama
Received 9 Dec 2013; first review completed 26 Dec 2013; accepted in final form 11 Feb 2014
Address reprint requests to Marcin F. Osuchowski, DVM, PhD, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstrasse 13A-1200 Vienna, Austria. E-mail: firstname.lastname@example.org.
Co-correspondence: Irshad H. Chaudry, PhD, Center for Surgical Research, University of Alabama at Birmingham, G094 Volker Hall, 1670 University Blvd, Birmingham, AL 35294. E-mail: Ichaudry@uab.edu.
The authors declare that no competing interests exist.