This PNAS paper has been featured in the lay press – from the New York Times in the US to Der Spiegel in Germany. Its major conclusion is indeed disturbing: ‘Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another.’
It should be noted that the findings cannot be simply generalized to other models and settings. Importantly, the authors have studied genomic responses of blood cells , not mechanisms directly related to the inflammatory stimulus (burn, trauma, etc.). In addition, only the genomic response of blood cells was assessed, not translation of these genes into proteins. In the discussion the authors ignore the existing literature, where a number of studies in candidate approaches have shown congruent (qualitatively and sometimes even qualitatively) responses in patient material and the corresponding mouse models (compare for example http://jem.rupress.org/content/198/5/725.long and http://stroke.ahajournals.org/content/39/1/237.long.)
Nevertheless, particularly with respect to immune cells in the blood there are obvious and drastic differences between mouse and man – sending blood from a healthy 1 month old mouse to a clinical routine laboratory would return the diagnosis of an acute lympatic neoplasia. Laboratory rodents are raised in a pathogen free environemt (SPF), their immune system is ‘untrained’, lymphatic, and immature.
Thus, Seok et al. expose an important caveat in the interpretation of rodent studies. There is an urgent need for translational research to use biomarkers to expose similarities and dissimilarities in the pathobiology of rodents and humans, as well as to improve the predictiveness of extrapolating from mouse to man with respect to responses to novel theapies. In addition, we need to increase the external validity of our models, by using rodents which have the same comorbidities, age, and environmental exposure as our patients.