B. Vickers1, C. Graham2, A. Chakraborti2, A. Moon2, J. Bibb2, G. Kennedy2 1Rhodes College,Memphis, TN, USA 2University Of Alabama at Birmingham,Gastrointestinal Surgery,Birmingham, Alabama, USA
Introduction: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic and relapsing inflammatory disorder of the intestine. Approximately 1 million Americans are currently diagnosed with IBD and as many as 70,000 new cases are diagnosed each year. One of the main factors contributing to IBD is stress, which has become a rampant problem in America and is considered a high-ranking health concern. Unfortunately, the relationship between IBD and stress has not been thoroughly investigated and the contributions of stress to IBD pathology are not well understood. We hypothesize that stress decreases susceptibility to intestinal inflammation.
Methods: To better understand the pathways that connect stress and IBD, C57Bl/6 mice were administered a Chronic Unpredictable Stress (CUS) regimen followed by 7 consecutive days of a subthreshold dose of Dextran Sodium Sulfate (DSS), a chemical inducer of colitis. After completion of CUS +/- DSS, animals were sacrificed, fecal samples were collected, and RNA was isolated from the proximal colon.
Results: To assess the effects of CUS and/or DSS on colon inflammation, an Enzyme-Linked Immunosorbent Assay (ELISA) was performed to quantify Lipocalin-2 (LCN-2) protein levels in fecal samples. We found that the LCN-2 levels in the CUS + DSS mice were significantly higher than control. Additionally, Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) was used to quantify mRNA transcript levels of three pro-inflammatory cytokines (IL-1β, IL-6, TNFα) in the proximal colon. Interestingly, CUS + DSS mice showed a significant increase in TNFα over control or either treatment alone.
Conclusion: We found that CUS and DSS alone failed to induce inflammation, but the combination of CUS and DSS showed a significant increase in colon inflammatory mediators suggesting that chronic stress may lower gut inflammatory threshold thereby increasing susceptibility to colitis. In the future, we plan to assess CUS in an IL10-/- colitis model as well as in the context of high fat/high carbohydrate diet.