Crohn disease, Inflammatory Bowel Disease

1,25-dihydroxyvitamin D3 and dexamethasone increase interleukin-10 production in CD4+ T cells from patients with Crohn's disease.

Bartels LE, Jørgensen SP, Agnholt J, Kelsen J, Hvas CL, Dahlerup JF.
Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, 8000 Aarhus C, Denmark. lebartels@gmail.com Int Immunopharmacol. 2007 Dec 15;7(13):1755-64. Epub 2007 Oct 5.

BACKGROUND AND AIM: In Crohn's disease (CD), epidemiological data and animal studies suggest that vitamin D (vitD) has protective immune-modulating properties. 1,25-dihydroxyvitamin D3 and dexamethasone (DEX) induce interleukin (IL)-10 productions in healthy controls (HC) T cells. We studied if 1,25-dihydroxyvitamin D3 with and without DEX could induce IL-10 production, downregulate pro-inflammatory Interferon (IFN)-gamma and Tumor Necrosis Factor (TNF)-alpha production, and influence cell kinetics in peripheral CD4+ T cells from CD patients.

METHODS: CD4+ T cells were separated from peripheral blood from CD patients and HC. Cells were activated by anti-CD3 and anti-CD28 in the presence of 1,25-dihydroxyvitamin D3 and/or DEX. Cytokine levels, proliferation, and apoptosis were measured following 7 days of culture.

RESULTS: In T cells from CD patients, 1,25-dihydroxyvitamin D3 and DEX increased IL-10 production from a median of 0.08 ng/ml to 0.2 ng/ml (p<0.01) and downregulated IFN-gamma production from 8.3 ng/ml to 3.1 ng/ml (p<0.01). The induced IL-10 increase in cultures from HC (0.2 ng/ml to 1.0 ng/ml, p<0.01) was significantly higher than in CD patients (p<0.05). In CD cultures, the IL-4 production increased from 0.3 ng/ml to 0.5 ng/ml (p<0.01) and IL-6 production from 2.5 ng/ml to 6.1 ng/ml (p<0.05). Similar changes in cytokine levels were observed with 1,25-dihydroxyvitamin D3 independently of DEX. In addition, 1,25-dihydroxyvitamin D3 and DEX decreased proliferation and reduced viability of T cells.

CONCLUSION: We found that 1,25-dihydroxyvitamin D3 with and without DEX stimulation increased IL-10 and reduced IFN-gamma production. These findings suggest that vitD may play a therapeutic role in CD.

Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?

Schoon EJ, Müller MC, Vermeer C, Schurgers LJ, Brummer RJ, Stockbrügger RW.
Department of Gastroenterology and Hepatology, University Hospital Maastricht, Maastricht, the Netherlands. ESCH@sint.azm.nl Gut. 2001 Apr;48(4):473-7.

BACKGROUND: A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency.

AIMS: To determine serum and bone vitamin K status in patients with Crohn's disease and to elucidate its relationship with bone mineral density.

METHODS: Bone mineral density was measured in 32 patients with longstanding Crohn's disease and small bowel involvement, currently in remission, and receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K, triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding capacity of osteocalcin was calculated. Data were compared with an age and sex matched control population.

RESULTS: Serum vitamin K levels of CD patients were significantly decreased compared with normal controls (p<0.01). "Free" osteocalcin was higher and hydroxyapatite binding capacity of circulating osteocalcin was lower than in matched controls (p<0.05 and p<0.001, respectively), indicating a low bone vitamin K status in Crohn's disease. In patients, an inverse correlation was found between "free" osteocalcin and lumbar spine bone mineral density (r=-0.375, p<0.05) and between "free" osteocalcin and the z score of the lumbar spine (r=-0.381, p<0.05). Multiple linear regression analysis showed that "free" osteocalcin was an independent risk factor for low bone mineral density of the lumbar spine whereas serum vitamin D was not.

CONCLUSIONS: The finding that a poor vitamin K status is associated with low bone mineral density in longstanding Crohn's disease may have implications for the prevention and treatment of osteoporosis in this disorder.