This thesis focuses on the development and analysis of mathematical models of acute inflammation. These models were developed to understand multiple organ dysfunction syndrome (MODS), which is a common cause of death in intensive care unit patients. MODS is characterized by sequential organ failure caused by an overactive immune system. Therefore, our modeling focused on the acute immune response, which is the generic initial response. Understanding the complex interaction during this response will facilitate the development of effective treatments for MODS.

We first derived a small scale model for the acute inflammation to understand simple dynamics between pro- and anti-inflammation. We use this reduced model to explore the role of anti-inflammatory mediators, which were once hypothesized as a treatment for MODS with less success than predicted. After the analysis of this reduced model, we expanded this model into two more complex models.

The first includes specific measurable immune mediators, unlike the four variable model. This model also takes in account the interactions between the tissue and blood, which are essential during an inflammatory response. It is a minimum model for an organ. We used this model to explore the spread of inflammation between organs by linking two tissues units to the same blood supply.

The second models the effects of inflammation on gas exchange in the lung. The lung is typically the first organ to fail during MODS. We developed a model for a single respiratory unit ∼25 alveoli). Linking the respiratory units (RUS) under various anatomical conditions we model the full lung. Methods were developed in order to reduce computation times of the RU model. With shorter computation times we were able to implement more accurate ventilation perfusion mismatch in the full model. To increase biological fidelity of the model we have created a closed loop form of the RU model that accounts for variable arterial PO₂ levels.

We have created multiple models that explore various aspects of MODS. We look at the role of anti-inflammation, spread of inflammation and inflammation within the lung in order to understand the complex interactions prompting organ failure.