Virginia Military Institute, Lexington, VA 24450, USA.
Bull Math Biol. 2010 May;72(4):765-79. doi: 10.1007/s11538-009-9468-9. Epub 2009 Oct 23.
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.
免疫系统功能障碍，由于遗传、疾病或环境因素，可能导致细菌定植和慢性炎症。在囊性纤维化和慢性阻塞性肺疾病中，呼吸道感染可引发气道炎症。我们提出了一个非线性常微分方程组系统来描述巨噬细胞、炎症和抗炎细胞因子以及细菌之间的相互作用。控制炎症细胞因子产生和巨噬细胞对细胞因子敏感性的参数的微小变化会导致模型行为的显著不同。当免疫系统正常运作时，非侵袭性病原体不会提供足够的触发因素引发慢性炎症，然而，在疾病中，炎症细胞因子的正反馈可以在细菌感染得到解决后引发慢性炎症。此外，如果巨噬细胞群体对炎症细胞因子更敏感，那么细菌引发的微小扰动也会导致慢性炎症。我们发现非侵袭性细菌能够引发慢性炎症，并提出为什么抗炎细胞因子治疗可能无法有效解决这种炎症。
