General Model of Inflammation

Abstract

Dysfunctions in the immune system, due to genetics, disease or environmental factors, can cause bacterial colonization and chronic inflammation. In cystic fibrosis and chronic obstructive pulmonary disease, respiratory infections can initiate inflammation of the airway. We propose a system of nonlinear ordinary differential equations to describe interactions between macrophages, both inflammatory and anti-inflammatory cytokines, and bacteria. Small changes in parameters governing inflammatory cytokine production and macrophage sensitivity to cytokines result in dramatically different model behaviors. When the immune system is functioning properly, a non-aggressive pathogen will not provide a sufficient trigger to initiate chronic inflammation, however, in disease positive feedback of the inflammatory cytokine can induce chronic inflammation even after a bacterial infection has been resolved. In addition, if the macrophage population is more sensitive to inflammatory cytokines small perturbations initiated by bacteria will also lead to chronic inflammation. We have found nonaggressive bacteria are able to initiate chronic inflammation and propose why anti-inflammatory cytokine therapy may not be effective in resolving this inflammation.

Integrated Inflammatory Stress (ITIS) Model

“…The elimination of endotoxin is proportional to the product of the number of activated phagocytic cells and the amount of endotoxin (Asachenkov et al 1994;Copeland et al 2005;Harrison et al 2011;Herald 2010;Loosbroock and Hunter 2014;Reynolds et al 2006;Vedder et al 1999;Zuev et al 2006). Thus, there will be no elimination of endotoxin if there is none of the activated phagocytic cells by this modeling choice.…”

Modelling the interaction between the host immune response, bacterial dynamics and inflammatory damage in comparison with immunomodulation and vaccination experiments

“…This is a simplification since the anti-inflammatory response is actually recruited by the inflammation. We make this simplifying assumption because the anti-inflammatory response should not be effective against the inflammation until macrophages (part of the pro-inflammatory response) are activated, similar to Herald (2010). This separate activation is the ‘reprogramming’ of already active macrophages by Treg cells.…”

“…The bacteria component (B) is treated as a growing population that benefits from inflammation—unlike previously mentioned models (Kumar et al , 2004; Reynolds et al , 2006; Herald, 2010) and is reduced by the pro-inflammatory response. We use logistic-type growth since we are not accounting for nutrient for the bacteria to harvest from the body where g is the growth rate.…”

“…In particular, the anti-inflammatory component was responsible for expanding the basin of attraction for the healthy steady state. In a similar model, the anti-inflammatory response was included to determine if the anti-inflammatory cytokines could be applied as a therapy to suppress chronic inflammation (Herald, 2010). These successful compartmental models are the groundwork for our current study.…”

Fractal immunology and immune patterning: Potential tools for immune protection and optimization

“…Likewise, T H 1-T H 2-T reg interactions in allergy and immunotherapy follow nonlinear dynamics (Gross et al, 2010). It has been suggested that general models of immune inflammation are most effectively modeled as reflecting nonlinear dynamics (Herald, 2010). In the case of host defense, Joh et al (2009) reported that prediction of disease outbreaks based on the interaction of environmental reservoirs of infectious agents and immune-based host defense follows nonlinear dynamics rather than more conventional linear alterations in equilibrium.…”