Wenjing Zhang, Sophia Jang, Colleen B Jonsson, Linda J S Allen
{"title":"病毒性人畜共患传染病炎症反应中的细胞因子动态模型。","authors":"Wenjing Zhang, Sophia Jang, Colleen B Jonsson, Linda J S Allen","doi":"10.1093/imammb/dqy009","DOIUrl":null,"url":null,"abstract":"<p><p>Inflammatory responses to an infection from a zoonotic pathogen, such as avian influenza viruses, hantaviruses and some coronaviruses, are distinctly different in their natural reservoir versus human host. While not as well studied in the natural reservoirs, the pro-inflammatory response and viral replication appear controlled and show no obvious pathology. In contrast, infection in humans results in an initial high viral load marked by an aggressive pro-inflammatory response known as a cytokine storm. The key difference in the course of the infection between the reservoir and human host is the inflammatory response. In this investigation, we apply a simple two-component differential equation model for pro-inflammatory and anti-inflammatory responses and a detailed mathematical analysis to identify specific regions in parameter space for single stable endemic equilibrium, bistability or periodic solutions. The extensions of the deterministic model to two stochastic models account for variability in responses seen at the cell (local) or tissue (global) levels. Numerical solutions of the stochastic models exhibit outcomes that are typical of a chronic infection in the natural reservoir or a cytokine storm in human infection. In the chronic infection, occasional flare-ups between high and low responses occur when model parameters are in a region of bistability or periodic solutions. The cytokine storm with a vigorous pro-inflammatory response and less vigorous anti-inflammatory response occurs in the parameter region for a single stable endemic equilibrium with a strong pro-inflammatory response. The results of the model analyses and the simulations are interpreted in terms of the functional role of the cytokines and the inflammatory responses seen in infection of the natural reservoir or of the human host.</p>","PeriodicalId":49863,"journal":{"name":"Mathematical Medicine and Biology-A Journal of the Ima","volume":null,"pages":null},"PeriodicalIF":0.8000,"publicationDate":"2019-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108568/pdf/dqy009.pdf","citationCount":"0","resultStr":"{\"title\":\"Models of cytokine dynamics in the inflammatory response of viral zoonotic infectious diseases.\",\"authors\":\"Wenjing Zhang, Sophia Jang, Colleen B Jonsson, Linda J S Allen\",\"doi\":\"10.1093/imammb/dqy009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Inflammatory responses to an infection from a zoonotic pathogen, such as avian influenza viruses, hantaviruses and some coronaviruses, are distinctly different in their natural reservoir versus human host. While not as well studied in the natural reservoirs, the pro-inflammatory response and viral replication appear controlled and show no obvious pathology. In contrast, infection in humans results in an initial high viral load marked by an aggressive pro-inflammatory response known as a cytokine storm. The key difference in the course of the infection between the reservoir and human host is the inflammatory response. In this investigation, we apply a simple two-component differential equation model for pro-inflammatory and anti-inflammatory responses and a detailed mathematical analysis to identify specific regions in parameter space for single stable endemic equilibrium, bistability or periodic solutions. The extensions of the deterministic model to two stochastic models account for variability in responses seen at the cell (local) or tissue (global) levels. Numerical solutions of the stochastic models exhibit outcomes that are typical of a chronic infection in the natural reservoir or a cytokine storm in human infection. In the chronic infection, occasional flare-ups between high and low responses occur when model parameters are in a region of bistability or periodic solutions. The cytokine storm with a vigorous pro-inflammatory response and less vigorous anti-inflammatory response occurs in the parameter region for a single stable endemic equilibrium with a strong pro-inflammatory response. The results of the model analyses and the simulations are interpreted in terms of the functional role of the cytokines and the inflammatory responses seen in infection of the natural reservoir or of the human host.</p>\",\"PeriodicalId\":49863,\"journal\":{\"name\":\"Mathematical Medicine and Biology-A Journal of the Ima\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.8000,\"publicationDate\":\"2019-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108568/pdf/dqy009.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mathematical Medicine and Biology-A Journal of the Ima\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1093/imammb/dqy009\",\"RegionNum\":4,\"RegionCategory\":\"数学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mathematical Medicine and Biology-A Journal of the Ima","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/imammb/dqy009","RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOLOGY","Score":null,"Total":0}
Models of cytokine dynamics in the inflammatory response of viral zoonotic infectious diseases.
Inflammatory responses to an infection from a zoonotic pathogen, such as avian influenza viruses, hantaviruses and some coronaviruses, are distinctly different in their natural reservoir versus human host. While not as well studied in the natural reservoirs, the pro-inflammatory response and viral replication appear controlled and show no obvious pathology. In contrast, infection in humans results in an initial high viral load marked by an aggressive pro-inflammatory response known as a cytokine storm. The key difference in the course of the infection between the reservoir and human host is the inflammatory response. In this investigation, we apply a simple two-component differential equation model for pro-inflammatory and anti-inflammatory responses and a detailed mathematical analysis to identify specific regions in parameter space for single stable endemic equilibrium, bistability or periodic solutions. The extensions of the deterministic model to two stochastic models account for variability in responses seen at the cell (local) or tissue (global) levels. Numerical solutions of the stochastic models exhibit outcomes that are typical of a chronic infection in the natural reservoir or a cytokine storm in human infection. In the chronic infection, occasional flare-ups between high and low responses occur when model parameters are in a region of bistability or periodic solutions. The cytokine storm with a vigorous pro-inflammatory response and less vigorous anti-inflammatory response occurs in the parameter region for a single stable endemic equilibrium with a strong pro-inflammatory response. The results of the model analyses and the simulations are interpreted in terms of the functional role of the cytokines and the inflammatory responses seen in infection of the natural reservoir or of the human host.
期刊介绍:
Formerly the IMA Journal of Mathematics Applied in Medicine and Biology.
Mathematical Medicine and Biology publishes original articles with a significant mathematical content addressing topics in medicine and biology. Papers exploiting modern developments in applied mathematics are particularly welcome. The biomedical relevance of mathematical models should be demonstrated clearly and validation by comparison against experiment is strongly encouraged.
The journal welcomes contributions relevant to any area of the life sciences including:
-biomechanics-
biophysics-
cell biology-
developmental biology-
ecology and the environment-
epidemiology-
immunology-
infectious diseases-
neuroscience-
pharmacology-
physiology-
population biology