Project description:Background/Purpose: Prior studies show an independent association between greater physical activity and lower inflammatory markers among adults in the general population, but the impact of physical activity on systemic inflammation in people with rheumatoid arthritis (RA) hasn’t been thoroughly investigated. We therefore aimed to determine whether physical activity behavior associates with differential expression of inflammatory genes in RA. Methods: Data derive from baseline assessments for a prospective observational cohort of patients with RA. At each study visit, we obtained detailed clinical information, collected peripheral whole blood for subsequent RNA sequencing (RNA-seq), and provided participants with actigraphs (GT9X ActiGraph Link device) to objectively measure physical activity by wearing the device at home for 7 consecutive 24-hour periods. Participants were categorized into three physical activity groups based on the highest (“active”), middle (“intermediate”), and lowest (“inactive”) tertiles for percentage of time spent in moderate/vigorous physical activity (metabolic equivalent (MET) level ≥2.00) across the sample. Results: There were 35 patients with complete clinical, actigraphy, and transcriptomic data available for analysis. The participants had a mean age of 56 years, were 90% female, and self-reported the following racial/ethnic identities: 32% white, 11% African American, 8% Asian, 40% Hispanic. Participants spent 48%, 41%, and 12% of time awake in sedentary, light, and moderate physical activity, respectively. None of the participants achieved vigorous activity. The patients in the most active group were younger but did not otherwise significantly differ by clinical and demographic characteristics compared to the other physical activity groups. However, in the differential gene expression analysis comparing the highest versus lowest physical activity tertiles, there were 365 up- and 402 down-regulated genes at an adjusted P value < 0.1. Gene set enrichment analysis revealed that the most physically active patients exhibited downregulation of diverse innate and adaptive immune signaling pathways. Assessment of upstream cytokine activation states demonstrated inhibition of type I, II and III interferons and activation of EPO in the highest physical activity tertile patients. Conclusion: Among a racially and ethnically diverse RA cohort, participants who spent more time in moderately intense physical activity had down-regulation of genes involved in both innate and adaptive immune signaling compared to those who were more sedentary. These findings provide mechanistic evidence to support a disease-modifying effect of physical activity in RA.

Project description:Baker2013 - Cytokine Mediated Inflammation in Rheumatoid Arthritis This model by Baker M. 2013, describes the interaction between pro and anti-inflammatory cytokine signalling in rheumatoid arthritis. Using two ordinary differential equations, the first model [BIOMD0000000550] analyses bifurcation and describes different pathological states by altering inflammatory regulation parameters. The second model [BIOMD0000000549] includes the effect that ageing has on pro-inflammatory signalling, allowing for time-dependant properties and disease progression to be observed. The author also describes potential dosing for reversal of the disease state. This model is described in the article: Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis. Baker M, Denman-Johnson S, Brook BS, Gaywood I, Owen MR. Math Med Biol 2013 Dec; 30(4): 311-337 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. This model is hosted on BioModels Database and identified by: BIOMD0000000550. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Baker2013 - Cytokine Mediated Inflammation in Rheumatoid Arthritis - Age Dependant This model by Baker M. 2013, describes the interaction between pro and anti-inflammatory cytokine signalling in rheumatoid arthritis. Using two ordinary differential equations, the first model [BIOMD0000000550] analyses bifurcation and describes different pathological states by altering inflammatory regulation parameters. The second model [BIOMD0000000549] includes the effect that ageing has on pro-inflammatory signalling, allowing for time-dependant properties and disease progression to be observed. The author also describes potential dosing for reversal of the disease state. This model is described in the article: Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis. Baker M, Denman-Johnson S, Brook BS, Gaywood I, Owen MR. Math Med Biol 2013 Dec; 30(4): 311-337 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. This model is hosted on BioModels Database and identified by: BIOMD0000000549. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Physical Activity Moderates Inflammatory Gene Expression in Rheumatoid Arthritis

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