TY - JOUR
T1 - Immunomodulatory effects of 1,25-dihydroxyvitamin D3 on Th1/Th2 cytokines in inflammatory bowel disease
T2 - An in vitro study
AU - Ardizzone, Sandro
AU - Cassinotti, A.
AU - Trabattoni, D.
AU - Manzionna, G.
AU - Rainone, V.
AU - Bevilacqua, M.
AU - Massari, A.
AU - Manes, G.
AU - Maconi, G.
AU - Clerici, M.
AU - Porro, G. Bianchi
PY - 2009/1
Y1 - 2009/1
N2 - Crohn's disease (CD) is associated with a higher type-1-helper T cell (Th1) cytokine expression, whereas ulcerative cotitis (UC) appears to express a modified Th2 response. In addition to its classic role in calcium homeostasis, calcitriol, the hormonal active form of vitamin D, exerts immunoregulatory effects such as modulation of Th1/Th2 cytokines. Therefore, calcitriol administration could modify immune dysfunction in CD and UC. Nine patients with UC [MIF: 5/4; mean age 47 years, remission(R)/active(A) disease: 7/2], 8 patients with CD [M/F: 2/6; mean age 36, R/A 5/3] and 6 healthy controls (HC) [M/F: 3/3, mean age 46] were enrolled. Peripheral blood was collected after a drug-washout of 15 days and peripheral blood mononuclear cells were stimulated with mitogens alone or in the presence of physiological concentrations of calcitriol (100 pg/ml). Type 1 (IL-2, TNF-α, IFN-γ) and type 2 (IL-10) cytokine production was assayed on supernatants by ELISA. Compared to HC, TNF-α production was significantly higher both in UC (p=0.0002) and CD (p=0.0001) patients, at baseline and after incubation with calcitriol (UC p=0.0003, CD p=0.0009). The effects of calcitriol incubation were: 1) reduced IFN-γ (p=0.024) and increased IL-10 (p=0.06) production in UC patients; 2) reduced TNF-α production in CD (p=0.032); 3) no significant effects in HC. Calcitriol increased, albeit not significantly, IL-10 production in UC compared to CD patients (p=0.09). These results suggest an important modulatory role of vitamin D in the Th1/Th2 immune response. The observation that the effect of this modulation was different in CD compared to UC patients provides an interesting area of research into the pathogenesis and treatment of these inflammatory conditions.
AB - Crohn's disease (CD) is associated with a higher type-1-helper T cell (Th1) cytokine expression, whereas ulcerative cotitis (UC) appears to express a modified Th2 response. In addition to its classic role in calcium homeostasis, calcitriol, the hormonal active form of vitamin D, exerts immunoregulatory effects such as modulation of Th1/Th2 cytokines. Therefore, calcitriol administration could modify immune dysfunction in CD and UC. Nine patients with UC [MIF: 5/4; mean age 47 years, remission(R)/active(A) disease: 7/2], 8 patients with CD [M/F: 2/6; mean age 36, R/A 5/3] and 6 healthy controls (HC) [M/F: 3/3, mean age 46] were enrolled. Peripheral blood was collected after a drug-washout of 15 days and peripheral blood mononuclear cells were stimulated with mitogens alone or in the presence of physiological concentrations of calcitriol (100 pg/ml). Type 1 (IL-2, TNF-α, IFN-γ) and type 2 (IL-10) cytokine production was assayed on supernatants by ELISA. Compared to HC, TNF-α production was significantly higher both in UC (p=0.0002) and CD (p=0.0001) patients, at baseline and after incubation with calcitriol (UC p=0.0003, CD p=0.0009). The effects of calcitriol incubation were: 1) reduced IFN-γ (p=0.024) and increased IL-10 (p=0.06) production in UC patients; 2) reduced TNF-α production in CD (p=0.032); 3) no significant effects in HC. Calcitriol increased, albeit not significantly, IL-10 production in UC compared to CD patients (p=0.09). These results suggest an important modulatory role of vitamin D in the Th1/Th2 immune response. The observation that the effect of this modulation was different in CD compared to UC patients provides an interesting area of research into the pathogenesis and treatment of these inflammatory conditions.
KW - Crohn's disease
KW - Th1
KW - Th2
KW - Ulcerative colitis
KW - Vitamin D
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M3 - Article
C2 - 19309553
AN - SCOPUS:62649107261
VL - 22
SP - 63
EP - 71
JO - International Journal of Immunopathology and Pharmacology
JF - International Journal of Immunopathology and Pharmacology
SN - 0394-6320
IS - 1
ER -