Sepsis is a state of disrupted inflammatory homeostasis that is often initiated by infection. It represents a very severe reaction of the immune system, activation of the pro-inflammatory cascades and the compensatory anti-inflammatory response. The resulting hemodynamic changes, microcirculatory disturbances and cellular disorders create a disparity between tissue perfusion and metabolic demands. The development and progression of sepsis is multi-factorial, and affects the cardiovascular, immunological and endocrine systems of the body. The complexity of sepsis makes the clinical sepsis study and sepsis therapeutics difficult.
Figure 1. The cascades of sepsis (Tyndall A, 2009).
Every year, an estimated 18 million people worldwide develop severe sepsis with an approximate 30 % death rate, which makes it a serious healthcare and social problem. Research of sepsis in humans is difficult due to the complexity of pathologic processes, heterogeneity of the affected population, lack of firmly established diagnostic markers, and restrictions of methodological and ethical nature. Taking into account the above difficulties, sepsis models in animals have been created and are valuable research tools. They provide a unique opportunity to elucidate the mechanisms of the disease and outline the capacity and specific approaches of therapeutic intervention.
Sepsis Models in Creative Animodel
Creative Animodel has successfully established some robust and reproducible sepsis animal models. Based on those models, we provide a set of preclinical services to evaluate the efficacy and safety of your drug candidates.
• LPS-induced Sepsis Model
Endotoxin or lipopolysaccharide (LPS), the principal component of the out membrane of Gram (-) bacteria, can stimulate the release of inflammatory mediators from various cell types, responsible for initiating the process of sepsis, including increase of pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6 and IL-8. This model is highly reproducible, easy to monitor by a variety of endpoints, and closely mimics clinical sepsis.
• CLP-induced Sepsis Model
The most widely used sepsis model is achieved by cecal ligation and puncture (CLP) which is recognized as one of the models with the greatest compatibility in clinical terms. With this sepsis model, the peritoneum is contaminated with mixed flora in the presence of devitalized tissue. This model, which can demonstrate apparent similarity to the clinical situation in perforated appendicitis or diverticulitis, is a robust and reproducible preclinical model of poly-microbial sepsis to facilitate drug screening. It can be used in a variety of different types of studies including development of antibiotics, antithrombotics, immune modifiers, and diagnostics.
Our Pharmacology Evaluation
We provide a package of preclinical evaluations for your drug candidates based on our sepsis models, including but not limited to:
• White blood cell counts
• Blood and tissue collection and colony forming unit (CFU) determination
• Cytokine/chemokine analysis
• Serum biochemistry assays
• PK/PD analyses
Creative Animodel spares no effort to create reproducible animal models for studying sepsis pathogenesis and preliminary testing of potential therapeutic agents. We have a team of scientists with profound pharmaceutical knowledge to support you in all aspects of new drug discovery and development. If you have any question, please feel free to contact us.
1. Popov D, Pavlov G. Sepsis models in experimental animals. Trakia Journal of Sciences, 2013, 11(1).
2. Tyndall A, Pistoia V. Mesenchymal stem cells combat sepsis. Nature medicine, 2009, 15(1): 18-20.