Lochhead Paul, Khalili Hamed, Ananthakrishnan Ashwin N, Richter James M, Chan Andrew T
Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Clin Gastroenterol Hepatol. 2016 Jun;14(6):818-824.e6. doi: 10.1016/j.cgh.2016.01.016. Epub 2016 Feb 1.
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).
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.
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).
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.
有证据表明免疫功能障碍在炎症性肠病（IBD）症状出现前数年就已存在。临床前全身炎症的特征描述有助于理解IBD的生物学特性，并最终促进早期疾病检测和干预策略的制定。我们评估了白细胞介素-6（IL6）和高敏C反应蛋白（hsCRP）的循环水平与新发克罗恩病（CD）或溃疡性结肠炎（UC）诊断之间的关联。
我们对参加两项基于人群的全国性前瞻性队列研究（护士健康研究和护士健康研究II）的参与者进行了巢式病例对照研究。我们分析了83例CD患者、90例UC患者和344例无IBD的匹配个体（对照对象）在诊断前采集的血样。测量了hsCRP和IL6的血浆水平。我们使用多变量逻辑回归模型研究每种炎症标志物与IBD风险之间的关联，以调整潜在的混杂暴露因素。
与IL6水平最低的五分位数相比，最高五分位数与CD的比值比（OR）为4.68（95%置信区间，1.91 - 11.46）（P趋势<0.001），与UC的OR为3.43（95%置信区间，1.44 - 8.15）（P趋势 = 0.004）。与hsCRP水平最低的五分位数相比，最高五分位数与CD的OR为2.82（95%置信区间，1.15 - 6.87）（P趋势 = 0.019），与UC的OR为1.79（95%置信区间，0.80 - 3.99）（P趋势 = 0.015）。
诊断前血浆中IL6和hsCRP水平与新发CD和UC的风险相关。全身炎症的亚临床水平可能是有症状IBD发生前早期疾病状态的一个特征。
