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


CONCLUSIONS
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.
Bartels
Lars Erik
LE
Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, 8000 Aarhus C, Denmark. lebartels@gmail.com
Jørgensen
Søren Peter
SP
Agnholt
Jørgen
J
Kelsen
Jens
J
Hvas
Christian Lodberg
CL
Dahlerup
Jens Frederik
JF
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002117:Calcitriol / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma; D002117:Calcitriol