Original Paper

Regulation of Cytokine Production in Human Peripheral Blood Mononuclear Cells and Allergen-Specific Th Cell Clones by 1,25-Dihydroxyvitamin D₃
Xiaohui Rausch-Fan^a, Fritz Leutmezer^a, Martin Willheim^a, Andreas Spittler^b, Barbara Bohle^a, Christof Ebner^a, Erika Jensen-Jarolim^a, George Boltz-Nitulescu<sup>a

a</sup>Institute of Pathophysiology, and
^bSurgical Research Laboratory, University of Vienna, Vienna, Austria

Address of Corresponding Author

Int Arch Allergy Immunol 2002;128:33-41 (DOI: 10.1159/000058001)

  Key Words

• Calcitriol
• Vitamin D₃
• Cytokines
• Lymphocytes
• Th clones

  Abstract

Background: The steroid hormone 1,25-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- and IL-12 by PBMC, as well as the percentage of CD4+ T cells containing intracytoplasmic IL-2 and IFN-. 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^-11M. Calcitriol diminished the secretion of IL-1, TNF-, and MG-CSF in PBMC. Furthermore, calcitriol also decreased the secretion of IL-2 and IFN- 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 1,25-dihydroxyvitamin D₃ may be used for new immunosuppressive therapies.

Copyright © 2002 S. Karger AG, Basel

  Author Contacts

Correspondence to: Dr. G. Boltz-Nitulescu
Institute of Pathophysiology
AKH-3Q, Währinger Gürtel 18-20
A-1090 Vienna (Austria)
Tel. +43 1 40400 5103, Fax +43 1 40400 5130, E-Mail georg.boltz@akh-wien.ac.at

  Article Information

Received: Received: January 29, 2001
Accepted after revision: February 14, 2002
Number of Print Pages : 9
Number of Figures : 5, Number of Tables : 1, Number of References : 46