Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Cytokine. 2018 Mar;103:38-45. doi: 10.1016/j.cyto.2017.12.023. Epub 2018 Jan 8.
BACKGROUND & AIMS: Vitamin D has immune modulating effects on cytokines. Serum vitamin D levels are associated with the risk of relapse in patients with ulcerative colitis (UC), through unknown mechanisms. We tested the hypothesis that this beneficial role of vitamin D on UC is mediated through anti-inflammatory serum cytokine profiles.
Serum samples from a prospective cohort of seventy UC patients in clinical remission were collected and baseline histological and endoscopic scores were recorded at enrollment. Clinical relapse events were recorded over the 12-month follow-up period. Serum vitamin D and cytokines levels (IL-6, IL-8, IL-17A, TNF-α, IFN-γ, IL-4, IL-10) were quantified using ELISA. Linear regression was used to determine correlation between vitamin D and cytokine profiles. Logistic regression models were used to determine the association between serum cytokine profiles and baseline histologic mucosal healing and clinical relapse.
Higher serum vitamin D levels positively correlated with higher ratios of IL-4 + IL-10/IL-17A + TNF-α (r = 0.37, P < .01), and IL-4 + IL-10/IL-6 + TNF-α (r = 0.32, P < .01). In multivariate analysis, IL-4 + IL-10/IL-17A + TNF-α ratios at baseline were associated with the presence of histologic mucosal healing (O.R. 1.29, 95% CI 1.02-1.62, P = .03). A higher ratio of serum IL-4 + IL-10 to IL-6 + TNF-α was associated with a reduced risk of clinical relapse (O.R. 0.72, 95% CI 0.58-0.89, P = .003), and longer time to relapse (p = .03), over the 12-month follow-up period. This ratio during remission had an AUC of 0.7 in predicting later clinical relapse.
Vitamin D is associated with anti-inflammatory serum cytokine profiles. Anti-inflammatory cytokine patterns may mediate the protective effects of higher serum vitamin D levels in patients with ulcerative colitis.
维生素 D 对细胞因子具有免疫调节作用。血清维生素 D 水平与溃疡性结肠炎（UC）患者的复发风险相关，但具体机制尚不清楚。我们假设维生素 D 对 UC 的这种有益作用是通过抗炎性血清细胞因子谱介导的。
收集了 70 例处于临床缓解期的 UC 患者前瞻性队列的血清样本，并在入组时记录基线组织学和内镜评分。在 12 个月的随访期间记录临床复发事件。使用 ELISA 定量测定血清维生素 D 和细胞因子水平（IL-6、IL-8、IL-17A、TNF-α、IFN-γ、IL-4、IL-10）。线性回归用于确定维生素 D 与细胞因子谱之间的相关性。逻辑回归模型用于确定血清细胞因子谱与基线组织学黏膜愈合和临床复发之间的关系。
较高的血清维生素 D 水平与较高的 IL-4+IL-10/IL-17A+TNF-α（r=0.37，P<.01）和 IL-4+IL-10/IL-6+TNF-α（r=0.32，P<.01）比值呈正相关。在多变量分析中，基线时 IL-4+IL-10/IL-17A+TNF-α 比值与组织学黏膜愈合有关（OR 1.29，95%CI 1.02-1.62，P=.03）。血清 IL-4+IL-10 与 IL-6+TNF-α 的比值较高与临床复发风险降低相关（OR 0.72，95%CI 0.58-0.89，P=.003），且在 12 个月的随访期间复发时间延长（P=.03）。在缓解期，该比值预测晚期临床复发的 AUC 为 0.7。
维生素 D 与抗炎性血清细胞因子谱相关。抗炎性细胞因子模式可能介导血清维生素 D 水平较高对溃疡性结肠炎患者的保护作用。
