The determination and its clinical significance of serum GM-CSF，IL-6，IL-17 and TNF-α in patients with rheumatoid arthritis

doi:10.3969/j.issn.1673-8640.2013.03.001

Abstract

Abstract: Objective　To determine the concentrations of serum granulocyte-macrophage colony stimulating factor(GM-CSF)，interleukin 6(IL-6)，interleukin 17(IL-17) and tumor necrosis factor-alpha(TNF-α)，and investigate their significance in the pathogenesis of rheumatoid arthritis(RA). Methods　A total of 81 RA outpatients were enrolled，including 36 inactive RA patients and 45 active RA patients，and 50 healthy subjects were as controls. Disease activity score 28(DAS28) of RA patients was evaluated，and the concentrations of serum GM-CSF，IL-6，IL-17 and TNF-α were determined by enzyme-linked immunosorbent assay(ELISA). The results were expressed as median(inter-quartile range). Results　The concentrations of serum GM-CSF were 12.7(9.7) pg/mL in inactive RA group，27.4(34.8) pg/mL in active RA group and 6.2(5.2) pg/mL in control group. The concentrations of serum IL-6 were 8.5(10.5)，47.1(43.8) and 4.7(5.3) pg/mL in the 3 groups，respectively. The concentrations of serum IL-17 were 19.3(16.4)，23.4(19.5) and 20.8(16.1) pg/mL in the 3 groups，respectively. The concentrations of serum TNF-α were 42.7(37.2)，76.2(42.4) and 34.1(21.9) pg/mL in the 3 groups，respectively. The concentrations of serum GM-CSF，IL-6 and TNF-α were higher in active RA group than in inactive RA group and control group(P＜0.01). The concentrations of serum GM-CSF，IL-6 and TNF-α were higher in inactive RA group than in control group(P＜0.05). IL-17 showed no statistical significance among the 3 groups(P＞0.05). GM-CSF was significantly correlated with IL-6 and TNF-α (r＝0.637 and 0.738 ，P＜0.001). There was no correlation between GM-CSF and IL-17 (r＝0.171，P＝0.426). In RA patients，there were correlations of DAS28 with GM-CSF，IL-6 and TNF-α (r＝0.583，0.656 and 0.758，P＜0.001). Conclusions　The concentrations of serum GM-CSF，IL-6 and TNF-α play important roles in RA pathogenesis. GM-CSF is a potential role in the regulation of IL-6 and TNF-α in RA patients.

Key words: Granulocyte-macrophage colony stimulating factor, Interleukin 6, Interleukin 17, Tumor necrosis factor-alpha, Rheumatoid arthritis

TANG Ronghua，HUANG Jianjun. The determination and its clinical significance of serum GM-CSF，IL-6，IL-17 and TNF-α in patients with rheumatoid arthritis[J]. , 2013, 28(3): 173-177.

References

[1]Smolen JS，Steiner G.Rheumatoid arthritis is more than cytokines: autoimmunity and rheumatoid arthritis[J]. Arthritis Rheum，2001，44(10):2218-2220.
[2]Steiner G，Smolen J. Autoantibodies in rheumatoid arthritis and their clinical significance[J]. Arthritis Res，2002，4（Suppl 2）:S1-S5.
[3]Firestein GS，Zvaifler NJ.How important are T cells in chronic rheumatoid synovitis ?: Ⅱ. T cell-independent mechanisms from beginning to end[J]. Arthritis Rheum，2002，46(2):298-308.
[4]Feldmann M. Development of anti-TNF therapy for rheumatoid arthritis[J]. Nat Rev Immunol，2002，2(5):364-371.
[5]Kunisada T，Miyazaki M，Mihara K，et al. A new human chondrosarcoma cell line (OUMS-27)that maintains chondrocytic differentiation[J]. Int J Cancer，1998，77(6):854-859.
[6]Altman R，Asch E，Bloch D，et al. Development of criteria for the classification and reporting of osteo-arthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association[J]. Arthritis Rheum，1986，29(8):1039-1049.
[7]Arnett FC，Edworthy SM，Bloch DA，et al. The American Rheumatism Association 1987 revised cri-teria for the classification of rheumatoid arthritis[J]. Arthritis Rheum，1988，31(3):315-324.
[8]Shimada S，Nakamura M，Tanaka Y. Crosslinking of the CD69 molecule enhances S100A9 production in activated neutrophils[J].Microbiol Immunol，2007，51(1):87-98.
[9]Tschesche H，Zlzer V，Triebel S，et al. The human neutrophil lipocalin supports the allosteric activation of matrix metalloproteinases[J]. Eur J Biochem，2001，268(7):1918-1928.
[10]Yan L，Borregaard N，Kjeldsen L，et al. The high molecular weight urinary matrix metalloproteinase(MMP) activity is a complex of gelatinase B/MMP-9 and neutrophil gelatinase-associated lipocalin(NGAL). Modulation of MMP-9 activity by NGAL[J]. J Biol Chem，2001，276(40):37258-37265.
[11]Koch G，Wagner T，Plater-Zyberk C，et al. Multi-response model for rheumatoid arthritis based on delay differential equations in collagen-induced arthritic mice treated with an anti-GM-CSF antibody [J]. J Pharmacokinet Pharmacodyn，2012，39 (1):55-65. 
[12]Nakano K，Okada Y，Saito K，et al. Rheumatoid synovial endothelial cells produce macrophage colony-stimulating factor leading to osteoclastogenesis in rheumatoid arthritis[J]. Rheumatology (Oxford)，2007，46(4):597-603. 
[13]Granet C，Miossec P. Combination of the pro-inflammatory cytokines IL-1，TNF-alpha and IL-17 leads to enhanced expression and additional recruitment of AP-1 family members，Egr-1 and NF-kappaB in osteoblast-like cells [J]. Cytokine，2004，26(4): 169-177.
[14]Bush KA，Farmer KM，Walker JS，et al.Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein[J].Arthritis Rheum，2002，46(3):802-805.
[15]Agarwal S，Misra R，Aggarwal A. Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metallo-proteinases[J].J Rheumatol，2008，35(3): 515-519.
[16]Sheibanie AF，Khayrullina T，Safadi FF，et al. Prostaglandin E2 exacerbates collagen-induced arthritis in mice through the inflammatory interleukin-23/ interleukin-17 axis[J]. Arthritis Rheum，2007，56(8):2608-2619.
[17]周兴辉，林连兵. 类风湿关节炎患者关节液血红素氧合酶-1水平的变化及临床意义[J].检验医学，2011，26（10）:672-674.
[18]Sylvester J，Liacini A，Li WQ，et al. Interleukin-17 signal transduction pathways implicated in inducing matrix metalloproteinase-3，-13 and aggrecanase-1 genes in articular chondrocytes[J]. Cell Signal，2004，16(4):469-476.
[19]Burrage PS，Mix KS，Brinckerhoff CE. Matrix metallo- proteinases: role in arthritis[J]. Front Biosci，2006，11:529-543.
[20]Kokkonen H，Sderstrm I，Rocklv J，et al. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis[J]. Arthritis Rheum，2010，62(2):383-391.
[21]Papatriantafyllou M. Cytokines: GM-CSF in focus[J]. Nat Rev Immunol，2011，11(6):370-371.