[1,25(OH)2-Vitamin-D3 attenuates Th17-related cytokines expression in peripheral blood mononuclear cells in patients with early-diagnosed rheumatoid arthritis]

Zhonghua Nei Ke Za Zhi. 2015 Apr;54(4):317-21.
[Article in Chinese]

Abstract

Objective: To investigate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] on T helper cell type 17 (Th17) cytokines and therapeutic mechanism in patients with rheumatoid arthritis (RA).

Methods: Peripheral blood mononuclear cells (PBMCs) from healthy donors and RA patients were collected. The PBMCs were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the absence or presence of 1,25(OH)₂D₃and methotrexate (MTX). After co-culture, the serum levels of Th17 cytokines interleukin (IL)-17, IL-6, tumour necrosis factor alpha (TNFα) were analyzed by cytometric bead array (CBA). The level of IL-22 was analyzed by enzyme-linked immunosorbent assay (ELISA). The independent samples t test and one-way analysis of variance (ANOVA) were used for statistical analysis.

Results: The levels of cytokines IL-17, TNFα, IL-6 and IL-22 in RA group were significantly higher than those in the control group [(43 ± 6)ng/L, (5.91 ± 2.53)ng/L, (16.6 ± 12.0)ng/L, (51 ± 17)ng/L vs (21 ± 3)ng/L, (2.63 ± 0.27)ng/L, (4.2±2.3)ng/L, (22 ± 14)ng/L]. Each of the three different 1,25(OH)₂D₃doses inhibited secretion of IL-17[(533 ± 47) pg/ml, (426 ± 55)pg/ml, (319 ± 86)pg/ml], TNFα[(424 ± 82)pg/ml, (382 ± 79)pg/ml, (326 ± 87)pg/ml], and IL-6[(5 513 ± 3 429)pg/ml, (4 555 ± 3 157)pg/ml, (3 748 ± 1 919)pg/ml] in RA group (P < 0.05), yet no statistical difference was found in IL-22 secretion with a trend of decrease after treatment of 1,25(OH)₂D₃. Three different doses of MTX inhibited secretion of IL-17 [(452 ± 50) pg/ml, (372 ± 67) pg/ml, (315 ± 104)pg/ml] and TNFα [(319 ± 74)pg/ml, (292 ± 59)pg/ml, (266 ± 64)pg/ml] in RA group (P < 0.05).However, levels of IL-6 and IL-22 were not affected after treated with MTX.

Conclusion: Our data indicated that 1,25(OH)₂D₃may play as an immune modulating agent to suppress Th17 cell cytokines. Supplement of vitamin D has the effective potential to treat patients with RA or other Th17 cell mediated autoimmune disorders.

MeSH terms

  • Antirheumatic Agents / pharmacology*
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Case-Control Studies
  • Cholecalciferol
  • Cytokines
  • Dose-Response Relationship, Drug
  • Early Diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Interleukin-6
  • Interleukins
  • Leukocytes, Mononuclear
  • Male
  • Methotrexate / pharmacology*
  • Middle Aged
  • RNA, Messenger / metabolism
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Tumor Necrosis Factor-alpha
  • Vitamin D / analogs & derivatives
  • Vitamins

Substances

  • Antirheumatic Agents
  • Cytokines
  • Interleukin-17
  • Interleukin-6
  • Interleukins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vitamins
  • dihydroxy-vitamin D3
  • Vitamin D
  • Cholecalciferol
  • interleukin-22
  • Methotrexate