Abstract

Association Between Circulating Levels of C-reactive Protein and Interleukin-6 and Risk of Inflammatory Bowel Disease

Lochhead P1, Khalili H1, Ananthakrishnan AN1, Richter JM2, Chan AT3. Clin Gastroenterol Hepatol. 2016 Feb 1. pii: S1542-3565(16)00108-7. doi: 10.1016/j.cgh.2016.01.016. [Epub ahead of print]
 
     
Author information

1Clinical and Translational Epidemiology Unit, Division of Medicine, Massachusetts General Hospital, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA. 2Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA. 3Clinical and Translational Epidemiology Unit, Division of Medicine, Massachusetts General Hospital, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Electronic address: achan@mgh.harvard.edu.

Abstract

BACKGROUND & AIMS: There is evidence that immune dysfunction precedes symptoms of inflammatory bowel disease (IBD) by several years. Characterization of preclinical systemic inflammation could contribute to our understanding of the biology of IBD and, ultimately, facilitate development of strategies for early disease detection and intervention. We evaluated associations between circulating levels of interleukin-6 (IL6) and high sensitivity C-reactive protein (hsCRP) and diagnosis of incident Crohn's disease (CD) or ulcerative colitis (UC).

METHODS: We conducted a nested case-control study of participants enrolled in 2 population-based, nationwide, prospective cohort studies (the Nurses' Health Study and the Nurses' Health Study II). We analyzed blood specimens, collected before diagnosis, from 83 persons with CD, 90 persons with UC, and 344 matched individuals without IBD (controls). Plasma levels of hsCRP and IL6 were measured. We investigated associations between each inflammatory marker and IBD risk using multivariable logistic regression models to adjust for potential confounding exposures.

RESULTS: Compared to the lowest quintile of IL6 level, the highest quintile was associated with an odds ratio (OR) of 4.68 (95% confidence interval, 1.91-11.46) for CD (Ptrend<.001) and an OR of 3.43 (95% confidence interval, 1.44-8.15) for UC (Ptrend=.004). The highest quintile of hsCRP level, compared to the lowest quintile, was associated with an OR of 2.82 (95% confidence interval, 1.15-6.87) for CD (Ptrend = 0.019) and an OR of 1.79 (95% confidence interval, 0.80-3.99) for UC (Ptrend = 0.015).

CONCLUSIONS: Plasma levels of IL6 and hsCRP before diagnosis are associated with risk of incident CD and UC. Subclinical levels of systemic inflammation may be a feature of an early disease state that precedes the development of symptomatic IBD.

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