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

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 the 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 (control subjects). 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 with 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 with the lowest quintile, was associated with an OR of 2.82 (95% confidence interval, 1.15-6.87) for CD (Ptrend = .019) and an OR of 1.79 (95% confidence interval, 0.80-3.99) for UC (Ptrend = .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.

SUBMITTER: Lochhead P

PROVIDER: S-EPMC4875875 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Lochhead Paul P Khalili Hamed H Ananthakrishnan Ashwin N AN Richter James M JM Chan Andrew T AT

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20160201 6

<h4>Background & aims</h4>There is evidence that immune dysfunction precedes symptoms of inflammatory bowel disease (IBD) by several years. Characterization of preclinical systemic inflammation could contribute to the 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 incid ...[more]

PMID: 26844874

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Project description:BackgroundPrevious studies that were based primarily on small numbers of patients suggested that certain circulating proinflammatory cytokines may be associated with lung cancer; however, large independent studies are lacking.MethodsAssociations between serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels and lung cancer were analyzed among 270 case patients and 296 control subjects participating in the National Cancer Institute-Maryland (NCI-MD) case-control study. Results were validated in 532 case patients and 595 control subjects in a nested case-control study within the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Association with C-reactive protein (CRP), a systemic inflammation biomarker, was also analyzed. Associations between biomarkers and lung cancer were estimated using logistic regression models adjusted for smoking, stage, histology, age, and sex. The 10-year standardized absolute risks of lung cancer were estimated using a weighted Cox regression model.ResultsSerum IL-6 and IL-8 levels in the highest quartile were associated with lung cancer in the NCI-MD study (IL-6, odds ratio [OR] = 3.29, 95% confidence interval [CI] = 1.88 to 5.77; IL-8, OR = 2.06, 95% CI = 1.19 to 3.57) and with lung cancer risk in the PLCO study (IL-6, OR = 1.48, 95% CI = 1.04 to 2.10; IL-8, OR = 1.57, 95% CI = 1.10 to 2.24), compared with the lowest quartile. In the PLCO study, increased IL-6 levels were only associated with lung cancer diagnosed within 2 years of blood collection, whereas increased IL-8 levels were associated with lung cancer diagnosed more than 2 years after blood collection (OR = 1.57, 95% CI = 1.15 to 2.13). The 10-year standardized absolute risks of lung cancer in the PLCO study were highest among current smokers with high IL-8 and CRP levels (absolute risk = 8.01%, 95% CI = 5.77% to 11.05%).ConclusionsAlthough increased levels of both serum IL-6 and IL-8 are associated with lung cancer, only IL-8 levels are associated with lung cancer risk several years before diagnosis. Combination of IL-8 and CRP are more robust biomarkers than either marker alone in predicting subsequent lung cancer.

Project description:BackgroundPrior epidemiological studies have established a correlation between inflammatory cytokines and inflammatory bowel disease (IBD). However, the nature of this relationship remains uncertain. Mendelian randomization (MR) study has the advantages of avoiding confounding and reverse causality compared with traditional observational research.ObjectiveWe aimed to evaluate whether genetically determined circulating levels of cytokines are associated with the risk of IBD by using the MR approach.Materials and methodsWe selected genetic variants associated with circulating levels of 28 cytokines at the genome-wide significance level from a genome-wide association study (GWAS) including 8,293 individuals. Summary-level data for IBD (including Crohn's disease and ulcerative colitis) were obtained from the International Inflammatory Bowel Disease Genetics Consortium and UK Biobank. We performed the primary analysis using the inverse-variance weighted method, as well as sensitivity analyses to test the stability of our results. We subsequently replicated the results of IBD in the UK Biobank dataset. A reverse MR analysis was also conducted to evaluate the possibility of reverse causation.ResultsGenetically predicted elevated levels of interleukin-17 (IL-17) and monokine induced by interferon-gamma (MIG) were associated with an increased risk of IBD[odds ratio (OR): 1.52, 95% confidence interval (CI):1.10-2.08, P =0.010 for IL-17 and OR: 1.58, 95% CI: 1.24-2.00, P = 1.60×10-4 for MIG]. Moreover, we observed suggestive associations between β-NGF and MIP-1β with the risk of Crohn's disease (OR: 0.71, 95% CI: 0.52-0.98, P = 0.039) and ulcerative colitis (OR: 1.08, 95% CI: 1.01-1.15, P= 0.019). In the reverse MR study, there was no evidence of causal effects of IBD and these cytokines.ConclusionOur study suggests the potential causal associations of IL-17 and MIG with IBD. Further studies are needed to determine whether IL-17 and MIG or their downstream effectors could be useful in the management of IBD.

Dataset Information

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

Publications

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

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