Higher serum vitamin D levels are associated with protective serum cytokine profiles in patients with ulcerative colitis

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. Methods: 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-alpha, IFN-gamma, 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. Results: Higher serum vitamin D levels positively correlated with higher ratios of IL-4 + IL-10/IL-17A + TNF-alpha (r = 0.37, P <.01), and IL-4 + IL-10/IL-6 + TNF-alpha (r = 0.32, P <.01). In multivariate analysis, IL-4 + IL-10/IL-17A + TNF-alpha 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-alpha was associated with a reduced risk of clinical relapse (O.R. 0.72, 95% Cl 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. Conclusions: 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.