03363nas a2200841   4500000000100000008004100001260001500042100001600057700001900073700001900092700002500111700001900136700001500155700002300170700002800193700001300221700001900234700002400253700002200277700001700299700002000316700002000336700002100356700001900377700002300396700001700419700002100436700002300457700002000480700002000500700002100520700002300541700002100564700002600585700002600611700002100637700002000658700001900678700002200697700002100719700002000740700002100760700002100781700002000802700001800822700002300840700009300863700001900956700002400975700001800999700001501017700002301032700002201055700001701077700002301094700002001117700001601137700002401153700002301177700002301200700002101223700001901244700002201263700001701285700001901302700001901321700001601340245007901356856005301435300001401488490000801502520101101510       2013                            d  c2013-02-261 aJunhee Seok1 aH. Shaw Warren1 aAlex G. Cuenca1 aMichael N. Mindrinos1 aHenry V. Baker1 aWeihong Xu1 aDaniel R. Richards1 aGrace P. McDonald-Smith1 aHong Gao1 aLaura Hennessy1 aCeleste C. Finnerty1 aCecilia M. López1 aShari Honari1 aErnest E. Moore1 aJoseph P. Minei1 aJoseph Cuschieri1 aPaul E. Bankey1 aJeffrey L. Johnson1 aJason Sperry1 aAvery B. Nathens1 aTimothy R. Billiar1 aMichael A. West1 aMarc G. Jeschke1 aMatthew B. Klein1 aRichard L. Gamelli1 aNicole S. Gibran1 aBernard H. Brownstein1 aCarol Miller-Graziano1 aSteve E. Calvano1 aPhilip H. Mason1 aJ. Perren Cobb1 aLaurence G. Rahme1 aStephen F. Lowry1 aRonald V. Maier1 aLyle L. Moldawer1 aDavid N. Herndon1 aRonald W. Davis1 aWenzhong Xiao1 aRonald G. Tompkins1 athe Inflammation and Host Response to Injury, Large Scale Collaborative Research Program1 aAmer Abouhamze1 aUlysses G. J. Balis1 aDavid G. Camp1 aAsit K. De1 aBrian G. Harbrecht1 aDouglas L. Hayden1 aAmit Kaushal1 aGrant E. O’Keefe1 aKenneth T. Kotz1 aWeijun Qian1 aDavid A. Schoenfeld1 aMichael B. Shapiro1 aGeoffrey M. Silver1 aRichard D. Smith1 aJohn D. Storey1 aRobert Tibshirani1 aMehmet Toner1 aJulie Wilhelmy1 aBram Wispelwey1 aWing H Wong00aGenomic responses in mouse models poorly mimic human inflammatory diseases  uhttps://www.pnas.org/doi/10.1073/pnas.1222878110  a3507-35120 v1103 aA cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. 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. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.