The acute inflammatory response in diverse shock states.
A poorly controlled acute inflammatory response can lead to organ dysfunction and death. Severe systemic inflammation can be induced and perpetuated by diverse insults such as the administration of toxic bacterial products (e.g., endotoxin), traumatic injury, and hemorrhage. Here, we probe whether these varied shock states can be explained by a universal inflammatory system that is initiated through different means and, once initiated, follows a course specified by the cellular and molecular mechanisms of the immune and endocrine systems. To examine this question, we developed a mathematical model incorporating major elements of the acute inflammatory response in C57Bl/6 mice, using input from experimental data. We found that a single model with different initiators including the autonomic system could describe the response to various insults. This model was able to predict a dose range of endotoxin at which mice would die despite having been calibrated only in nonlethal inflammatory paradigms. These results show that the complex biology of inflammation can be modeled and supports the hypothesis that shock states induced by a range of physiologic challenges could arise from a universal response that is differently initiated and modulated.
Chow
Carson C
CC
Department of Mathematics, University of Pittsburgh, Pittsburgh, Pensylvania 15261, USA.
Clermont
Gilles
G
Kumar
Rukmini
R
Lagoa
Claudio
C
Tawadrous
Zacharia
Z
Gallo
David
D
Betten
Binnie
B
Bartels
John
J
Constantine
Gregory
G
Fink
Mitchell P
MP
Billiar
Timothy R
TR
Vodovotz
Yoram
Y
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000473:pathology; D006470:Hemorrhage / Q000473:pathology; D007249:Inflammation / Q000097:blood / Q000150:complications; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009569:Nitric Oxide / Q000096:biosynthesis; D012769:Shock / Q000097:blood* / Q000150:complications* / Q000276:immunology / Q000473:pathology; D014947:Wounds and Injuries / Q000473:pathology
D016753:Interleukin-10; D009569:Nitric Oxide