A reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administration

被引:103
作者
Day, Judy
Rubin, Jonathan
Vodovotz, Yoram
Chow, Carson C.
Reynolds, Angela
Clermont, Gilles
机构
[1] Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA
[2] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA
[3] CIRM, Pittsburgh, PA 15219 USA
[4] Univ Pittsburgh, CRISMA Lab, Pittsburgh, PA 15261 USA
[5] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA
[6] Univ Pittsburgh, Med Ctr, Dept Crit Care Med, Pittsburgh, PA 15261 USA
关键词
immunology; mathematical modeling; anti-inflammatory cytokines; endotoxin tolerance; inflammation;
D O I
10.1016/j.jtbi.2006.02.015
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:237 / 256
页数:20
相关论文
共 65 条
[1]   Bacterial lipopolysaccharides and innate immunity [J].
Alexander, C ;
Rietschel, ET .
JOURNAL OF ENDOTOXIN RESEARCH, 2001, 7 (03) :167-202
[2]   Interleukin-1β induces in vivo tolerance to lipopolysaccharide in mice [J].
Alves-Rosa, F ;
Vulcano, M ;
Beigier-Bompadre, M ;
Fernández, G ;
Palermo, M ;
Isturiz, MA .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2002, 128 (02) :221-228
[3]   High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes [J].
Andersson, U ;
Wang, HC ;
Palmblad, K ;
Aveberger, AC ;
Bloom, O ;
Erlandsson-Harris, H ;
Janson, A ;
Kokkola, R ;
Zhang, MH ;
Yang, H ;
Tracey, KJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (04) :565-570
[4]  
BACON GE, 1973, JOHNS HOPKINS MED J, V132, P127
[5]  
Balkhy HH, 1999, J IMMUNOL, V162, P3633
[7]   INTERLEUKIN-10 IS A CENTRAL REGULATOR OF THE RESPONSE TO LPS IN MURINE MODELS OF ENDOTOXIC-SHOCK AND THE SHWARTZMAN REACTION BUT NOT ENDOTOXIN TOLERANCE [J].
BERG, DJ ;
KUHN, R ;
RAJEWSKY, K ;
MULLER, W ;
MENON, S ;
DAVIDSON, N ;
GRUNIG, G ;
RENNICK, D .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (05) :2339-2347
[9]  
Bogdan C, 2000, PROG INFLAM RES, P217
[10]   Effects of repeated injections of interleukin 1β or lipopolysaccharide on the HPA axis in the newborn rat [J].
Bumiller, A ;
Götz, F ;
Rohde, W ;
Dörner, G .
CYTOKINE, 1999, 11 (03) :225-230