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P344 Vitamin D-Induced alterations in Cytokine levels lower the risk of clinical relapse in ulcerative colitis

Gubatan J.M., Mitsuhashi S., Longhi M.S., Zenlea T., Rosenberg L., Robson S., Moss A.

Beth Israel Deaconess Medical Center, Harvard Medical School, Division of Gastroenterology, Department of Medicine, Boston, United States

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).

Figure 1

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).

Figure 2

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).

Conclusion

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.