Regulation of cytokine production in human peripheral blood mononuclear cells and allergen-specific th cell clones by 1alpha,25-dihydroxyvitamin D3.
BACKGROUND
The steroid hormone 1alpha,25-dihydroxyvitamin D3 (calcitriol), in addition to its crucial role in calcium homeostasis, exerts several effects on the immune system by regulating cell proliferation, differentiation, and maturation. These effects may be exerted through the control of protooncogenes and the regulation of cytokine production.


METHODS
The influence of calcitriol on cytokines secretion by human peripheral blood mononuclear cells (PBMC) isolated from healthy donors, and by allergen-specific T helper (Th) cell clones was studied. PBMC were cultured for 48 h with phorbol myristate acetate (PMA) and ionomycin in the presence or absence of calcitriol. Human Th cell clones were stimulated with either Bet v 1 allergen or anti-CD3 antibodies and PMA. Cytokines were measured in the supernatants by ELISA, and at single-cell level by FACS.


RESULTS
Calcitriol significantly inhibited the production of IL-2, IFN-gamma and IL-12 by PBMC, as well as the percentage of CD4+ T cells containing intracytoplasmic IL-2 and IFN-gamma. Interestingly, calcitriol-treated PBMC induced the production of IL-10 and IL-5, but not of IL-4. The effect of calcitriol was maximal at 10(-7) to 10(-9) and noneffective at 10(-11) M. Calcitriol diminished the secretion of IL-1, TNF-alpha, and MG-CSF in PBMC. Furthermore, calcitriol also decreased the secretion of IL-2 and IFN-gamma by Th1 clones, and of IL-4 by Th2 clones.


CONCLUSIONS
Our data strongly support the notion that calcitriol modulates the production of cytokines in a time- and concentration-dependent manner, and suggest that nonhypercalcemic derivatives of 1alpha,25-dihydroxyvitamin D(3) may be used for new immunosuppressive therapies.
Rausch-Fan
Xiahoui
X
Institute of Pathophysiology, University of Vienna, Vienna, Austria.
Leutmezer
Fritz
F
Willheim
Martin
M
Spittler
Andreas
A
Bohle
Barbara
B
Ebner
Christof
C
Jensen-Jarolim
Erika
E
Boltz-Nitulescu
George
G
D000485:Allergens / Q000276:immunology; D052179:Antigens, Plant; D002117:Calcitriol / Q000276:immunology* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016853:Muromonab-CD3 / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D016853:Muromonab-CD3; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula; D002117:Calcitriol