A reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administration.
Bacterial lipopolysaccharide (LPS; endotoxin) is a potent immunostimulant that can induce an acute inflammatory response comparable to a bacterial infection. Experimental observations demonstrate that this biological response can be either blunted (tolerance) or augmented (potentiation) with repeated administration of endotoxin. Both phenomena are of clinical relevance. We show that a four-dimensional differential equation model of this response reproduces many scenarios involving repeated endotoxin administration. In particular, the model can display both tolerance and potentiation from a single parameter set, under different administration scenarios. The key determinants of the outcome of our simulations are the relative time-scales of model components. These findings support the hypothesis that endotoxin tolerance and other related phenomena can be considered as dynamic manifestations of a unified acute inflammatory response, and offer specific predictions related to the dynamics of this response to endotoxin.
Day
Judy
J
Department of Mathematics, 301 Thackeray, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Rubin
Jonathan
J
Vodovotz
Yoram
Y
Chow
Carson C
CC
Reynolds
Angela
A
Clermont
Gilles
G
D000208:Acute Disease; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D003198:Computer Simulation; D007109:Immunity; D008070:Lipopolysaccharides / Q000276:immunology*; D018448:Models, Immunological; D012008:Recurrence
D008070:Lipopolysaccharides