Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis

Math Med Biol. 2013 Dec;30(4):311-37. doi: 10.1093/imammb/dqs026. Epub 2012 Sep 20.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease preferentially affecting the joints and leading, if untreated, to progressive joint damage and disability. Cytokines, a group of small inducible proteins, which act as intercellular messengers, are key regulators of the inflammation that characterizes RA. They can be classified into pro-inflammatory and anti-inflammatory groups. Numerous cytokines have been implicated in the regulation of RA with complex up and down regulatory interactions. This paper considers a two-variable model for the interactions between pro-inflammatory and anti-inflammatory cytokines, and demonstrates that mathematical modelling may be used to investigate the involvement of cytokines in the disease process. The model displays a range of possible behaviours, such as bistability and oscillations, which are strongly reminiscent of the behaviour of RA e.g. genetic susceptibility and remitting-relapsing disease. We also show that the dose regimen as well as the dose level are important factors in RA treatments.

Keywords: ODE; anti-inflammatory; cytokines; mathematical modelling; pro-inflammatory; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • Computer Simulation
  • Cytokines / antagonists & inhibitors
  • Cytokines / immunology*
  • Female
  • Humans
  • Inflammation / drug therapy
  • Inflammation / immunology*
  • Inflammation Mediators / therapeutic use*
  • Male
  • Models, Immunological*

Substances

  • Cytokines
  • Inflammation Mediators