Background: Vitamin D has immunomodulatory effects in vitro, and we have previously associated serum levels with clinical outcomes in ulcerative colitis (UC). We sought to investigate a biological explanation for this link.
Methods: The effects of 1,25-hydroxyvitamin D on cytokine mRNA and protein levels were evaluated in human colonic epithelial cells (DLD1) challenged with lipopolysaccharide in vitro. Serum vitamin D and cytokine levels were measured at baseline in a prospective cohort of UC patients (N=70) in clinical remission, and correlated with risk of relapse within 12 months using logistic regression models.
Results: Vitamin D (10 nM) stimulated increased IL-10, and decreased TNF-α, levels in colonic epithelial cells in vitro. In patients, higher vitamin D positively correlated with the ratio of anti-inflammatory-to-pro-inflammatory cytokine levels in serum (IL-4+IL-10/IL-6+TNF-α, r=0.3249, p<0.01).
This ratio (IL-4+IL-10/IL-6+TNF-α) was higher at baseline among patients who remained in clinical remission over 12 months (mean 24 in remitters vs 13 in relapsers, p<0.05).
This association with future risk of clinical relapse persisted when endoscopic and histological inflammation at baseline were controlled for in a multivariate model (O.R. 0.7, 95% CI 0.6–0.9, p=0.003).
Conclusions: Vitamin D induces an anti-inflammatory cytokine profile that is more prevalent in patients with UC who exhibit sustained clinical remission. Such immunomodulatory properties warrant further examination for therapeutic potential.