Analyzing inflammatory response as excitable media

The regulatory system of the transcription factor NF-κB plays a great role in many cell functions, including inflammatory response. Interestingly, the NF-κB system is known to up-regulate production of its own triggering signal-namely, inflammatory cytokines such as TNF, IL-1, and IL-6. In this paper we investigate a previously presented model of the NF-κB, which includes both spatial effects and the positive feedback from cytokines. The model exhibits the properties of an excitable medium and has the ability to propagate waves of high cytokine concentration. These waves represent an optimal way of sending an inflammatory signal through the tissue as they create a chemotactic signal able to recruit neutrophils to the site of infection. The simple model displays three qualitatively different states; low stimuli leads to no or very little response. Intermediate stimuli leads to reoccurring waves of high cytokine concentration. Finally, high stimuli leads to a sustained high cytokine concentration, a scenario which is toxic for the tissue cells and corresponds to chronic inflammation. Due to the few variables of the simple model, we are able to perform a phase-space analysis leading to a detailed understanding of the functional form of the model and its limitations. The spatial effects of the model contribute to the robustness of the cytokine wave formation and propagation.