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


CONCLUSIONS
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.
Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China; Email: wenhongyan0509@aliyun.com.
Hongyan
H
Wen
Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
Jing
J
Luo
Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
Xiaoying
X
Zhang
Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
Chen
C
Zhang
Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
Xiangcong
X
Zhao
Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
Xin
X
Wang
Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
Xiaofeng
X
Li
D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D016022:Case-Control Studies; D002762:Cholecalciferol; D016207:Cytokines; D004305:Dose-Response Relationship, Drug; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6; D007378:Interleukins; D007963:Leukocytes, Mononuclear; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D / Q000031:analogs & derivatives; D014815:Vitamins; D000097043:Interleukin-22
D018501:Antirheumatic Agents; D002762:Cholecalciferol; D016207:Cytokines; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D008727:Methotrexate; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D; D014815:Vitamins; D000097043:Interleukin-22; C118756:dihydroxy-vitamin D3