僵直性脊椎炎的華人使用恩博治療後血清細胞白介素-6和基質金屬蛋白酶-3顯著降低

Signifi cant decrease in serum IL-6 and MMP-3 after etanercept treatment in ankylosing spondylitis patients

目的：評估僵直性脊椎炎的華人使用恩博治療前後，血清中細胞激素和發炎相關物質的變化。方法：14位患有僵直性脊椎炎的華人接受12週的恩博治療（25毫克，一週兩次），於治療前後測量血清中的腫瘤壞死因子-α、細胞白介素-1、細胞白介素-6，細胞白介素-8、細胞白介素-10、轉化生長因子-β、腫瘤壞死因子相關細胞凋亡誘導配體（TRAIL）、和基質金屬蛋白酶（MMP）。週邊血液單核細胞上的類鐸受體-2（Toll-like receptor 2,TLR-2）和類鐸受體-4（TLR-4）用流式細胞儀染色。結果：經過3個月的恩博治療，病患血中的腫瘤壞死因子-α從一開始量不到，到明顯增加，但各個月的值沒有明顯統計差異。細胞白介素-6濃度在經過治療後明顯下降（14.2 ± 14.5 pg/mL vs. 3M, 4.0 ± 2.8 pg/mL, p=0.001）；同時，血清中的基質金屬蛋白酶-3在治療後也是明顯減少（42.2 ± 29.7 ng/mL vs. 3M, 28.6 ± 26.5 ng/mL, p=0.005）。細胞白介素-1和細胞白介素-8測量不到；細胞白介素-10、轉化生長因子-β、和腫瘤壞死因子相關細胞凋亡誘導配體的濃度沒甚麼變化；而週邊血液單核細胞上表現的類鐸受體-2和類鐸受體-4在經過治療後下降，但沒有明顯差異。結論：僵直性脊椎炎經過短期恩博治療後，血清中的細胞白介素-6和基質金屬蛋白酶-3會顯著下降。

Objective: To evaluate the changes in the level of serum cytokines and infl ammation-related mediators before and after etanercept treatment in patients with ankylosing spondylitis (AS). Methods: In an open-label 12-week trial of etanercept (25 mg twice per week) in ethnic Chinese patients with AS, 14 subjects received laboratory tests before and after etanercept. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), transforming growth factor-β (TGF-β), TNF-related apoptosis-inducing ligand (TRAIL) and matrix metalloproteinase (MMP) were measured by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells (PBMC) were stained for toll-like receptor (TLR) 2 and 4, using fl ow cytometry. Results: Before and 3 months after etanercept treatment, the results showed TNF-α was not detectable at baseline, but significantly increased after etanercept treatment for 2 weeks; however, there was no significant change from month to month. IL-6 in the serum was not very high at baseline, but it was signifi cantly reduced after etanercept treatment (baseline, 14.2 ± 14.5 pg/mL vs. 3 months 4.0 ± 2.8 pg/ mL, p=0.001). Like IL-6, MMP-3 also decreased signifi cantly after etanercept treatment (baseline 42.2 ± 29.7 ng/mL vs. 3 months 28.6 ± 26.5 ng/mL, p=0.005). IL-1 and IL-8 were not detected. IL-10, TGF-β, and TRAIL levels showed no change. The expression of TLR-2 and TLR-4 on PBMC decreased after 12 weeks, but this was not signifi cant. Conclusion: Serum levels of IL-6 and MMP-3 were signifi cantly decreased after short-term etanercept therapy.