| Abstract: |
| Inflammatory response in pathogen infections has distinct differences in humans and their natural reservoirs for Avian Influenza, Dengue, Hantavirus, and SARS-CoV. Taking Hantaviruses for example, the infection persists in natural rodent reservoirs and may last the life of the animal. While the spillover infection to humans results in severe, life threatening disease, such as acute lung injury, respiratory failure, sepsis, and a cytokine storm. Simple ODE and SDE models with pro-inflammatory and anti- inflammatory cytokines are studied to investigate underlying causes and reveal potential mechanisms. The bifurcation analysis on ODE model demonstrates an array of dynamical behaviors of the inflam- matory response in pathogen infections. With the increase of the control efforts from anti-inflammatory cytokines, (1) pro-inflammatory cytokines first stabilizes in high level concentration, (2) they have the possibility to drop to a low level concentration showing bistability, (3) then they oscillate between low and high level concentrations, (4) further they spend a longer time in the low concentration with periodic flare-ups. Further random changes are considered in two corresponding stochastic differential equations (SDE) models. The SDE simulations show flare-ups in pro-inflammatory cytokines concen- tration with the same input of parameter values and initial conditions generating bistable behavior in the deterministic ODE model. Furthermore, the uniform period and amplitude of recurrent cycles produced from the ODE model become time-varying in the simulation of SDE model. The analysis results demonstrate the distinct inflammatory responses in pathogen infections in human and non- human species due to interactions between pro- and anti-inflammatory cytokines. These findings are consistent with the fact that people with healthy immune systems are more likely to produce high levels of pro-inflammatory cytokines in infection, thereby initiate cytokine storm. The results also give an potential explanation to no significant symptom in Hantavirus natural rodent reservoirs. |
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