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Term Paper Introduction
A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammation.
Angela Reynolds et. al.
The world is full of germs, known as pathogens. Pathogens are microbes or microorganisms such as a viruses, bacterium, prions, or fungi that causes disease in an animal or plant host.  In humans, pathogens are particularly concerning because they lead to an inflammatory response in our bodies . When the body is infected, it mounts an initial immune response, known as the acute inflammatory response, to rid itself of the pathogens and restore health.  In a healthy response, the inflammatory response becomes activated, clears the pathogen (in the event of infection), begins a repair process and stops.  Uncontrolled acute inflammation due to infection is defined clinically as sepsis and can culminate in organ failure and death.  Death can occur in two possible ways: “septic death” or “aseptic death.” The aseptic death state corresponds to an outcome where pathogen has been eliminated but with high and persistent immune activation and damage.  The septic death state corresponds to a state in which there is insufficient immune activation to clear pathogen. 
Septic death occurs when the acute immune response generates uncontrolled inflammation, which leads to severe tissue damage, and the pathogen is not eliminated either. Suffering from uncontrolled inflammation due to a infection is called “sepsis”. Sepsis is a common condition but it is fatal. It is characterized by a systemic inflammatory response and is seen in association with a large number of clinical conditions. Severe sepsis occurs in more than 750 000 individuals in the United States each year, with a hospital mortality of about 30%.  Current clinical treatments for sepsis are utilizing antibiotics, surgery to remove the source of the infection, and utilizing corticosteroids.  Despite the use of these therapies, the mortality rates of patients with sepsis remains high. One reason for the lack of effective treatments may be that the complex nature of the inflammatory response renders the effect of targeting isolated components of inflammation difficult to predict. Another complication stems from how the initial progression of systemic inflammation can have different manifestations depending on how it is triggered, i.e., infection or trauma. Understanding the complexities of the inflammatory response is important for developing a treatment for sepsis.
Much research has been devoted to understanding the immune systems, in particular, the acute immune response. Advances in understanding the host immune response have fueled considerable interest finding a definitive solution to sepsis mortality. Day et al. completed an experiment which considers scenarios of repeated endotoxin administration to purposefully induce sepsis in animal models. Their results showed the the administration of the second dose of endotoxins was time dependent; at certain points in the immune response the body had recovered enough to fight the secondary wave of endotoxins. A particularly notable paper, which provides further insight into the time-dependency of the acute immune system, is "A reduced mathematical model of the acute inflammatory response: Derivation of model and analysis of anti-inflammation" written by Reynolds et al.  The authors constructed a model of the body's inflammatory response and included a time dependent anti-inflammatory response. The hypothesis proposed by Reynolds et. al. is that a time-dependent anti-inflammatory response results in a healthy immune response, compared to a static anti-inflammatory response, and the time-dependent anti-inflammatory response is characterized by a more stable equilibrium between aseptic and septic death which defines the healthy state. Our reproduction of the model will seek to verify this hypothesis and show that the timing of the anti-inflammatory mediator is crucial. The results of Reynold's paper illustrate that the point at which administration of an anti-inflammatory mediator occurs during the response to an infection may compromise outcome. This paper by Reynolds, et al. provides new insight into the inflammatory response and offers possible sepsis treatments which may be effective due to the new knowledge of the acute inflammatory response.
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