Sepsis animal models

IL-lra (17.5) Monocyte/macrophage, fibroblast Specifically inhibits IL-1 effects, including SIRS and sepsis in animal models and humans. Attenuation of coagulation, fibrinolytic, and complement systems, levels of PAF and neutrophil elastase. 

Deitch, E. A. (1998) Animal models of sepsis and shock a review and lessons learned. Shock 9, 1-11. 

Early reports with rAd vectors may provide the proof of principle for transient expression of a number of potentially therapeutic proteins. For instance the Na+/K+-ATPase was found to promote reabsorption of alveolar fluid in an ARDS model (Factor et al., 1999 Sartori and Matthay, 2002). Anti-inflammatory cytokines and antioxidants have also been used with some success in a similar context in animal models of sepsis and ARDS (Van Laethem et al., 1998 Dumasius et al., 2002). 

The time-line of events in sepsis in both animal models and human sepsis as well as the window for treatments targeting endotoxin are shown in Fig. 15.1. 

In animal studies on endotoxin-induced sepsis, raising HDL or administering human HDL and/or other lipoproteins reduced mortality (Harris et al., 1990 Levine et al., 1993). Using a hypolipemic animal model an increase in cytokine production and mortality with endotoxin challenge has been demonstrated (Feingold et al., 1995). After lipoprotein administration, the authors showed the mortality return to the same level as the control group. 

Bacteria The choice of bacteria for animal models of sepsis depends on the goals of the study. We have used Escherichia coli, because it is one of the most common clinical isolates in humans with sepsis (5). The K-l serotype is associated with invasive infection in humans and rabbits. Bacteria are thawed from a frozen stock and inoculated into 50 mL Lennox-B broth, then grown overnight to stationary phase at 37°C with continuous stirring. After overnight incubation, the... 

Chemical modification of the unfiactionated heparin, such as desul tion, deamination and coupling with various agents have resulted in products of non-anticoagulant nature with selective actions on enzymes and cellular receptors. Thioxyloside derivatives have also been reported to produce oral antithrombotic actions in animal models. However, relatively larger dosages are needed to produce these effects. These heparin derivatives are currently tested for such indications as sepsis, viral infections and the treatment of proliferative disorders. 

Whether or not Hb accentuates lethal effects of endotoxin is also not resolved. When inoculation with living E. coli or endotoxin has been used to induce sepsis in mice, some Hb preparations have been found to demonstrate deleterious effects. " In contrast, other studies using better characterized, modified Hb solutions have failed to confirm these findings, both in mice and in other animal models. ... 

Some animal models of sepsis are shown in Table 4. 

Animal disease models for acquired AT deficiency, such as Escherichia cofi-induced sepsis, were used to assess the biological consistency of the rhAT compared to hpAT. Although in these models the exact contributions of the anti-coagulant and anti-inflammatory properties of AT are still somewhat controversial [81], they do allow for some comparison of the properties of rhAT with hpAT. Human plasma-derived AT has been shown to prevent the lethal effects of experimentally induced sepsis in several animal models [82-89], and to block cytokine production in vitro. To date, several dose- response studies have been performed with rhAT in rats (GTC Biother-... 

---