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抗肿瘤坏死因子(TNF)α治疗类风湿性关节炎(英夫利昔单抗)可选择性下调白细胞介素(IL)18的产生,但不会下调IL12和IL13的产生。

Anti-tumour necrosis factor (TNF) alpha treatment of rheumatoid arthritis (infliximab) selectively down regulates the production of interleukin (IL) 18 but not of IL12 and IL13.

作者信息

Pittoni V, Bombardieri M, Spinelli F R, Scrivo R, Alessandri C, Conti F, Spadaro A, Valesini G

机构信息

Dipartimento di Terapia Medica, Cattedra di Reumatologia, Università La Sapienza, Roma, Italy.

出版信息

Ann Rheum Dis. 2002 Aug;61(8):723-5. doi: 10.1136/ard.61.8.723.

Abstract

OBJECTIVE

To measure interleukin (IL)18 serum concentrations in patients with rheumatoid arthritis (RA) undergoing infliximab treatment (tumour necrosis factor (TNF) alpha blockade) and to evaluate the concomitant modification of IL12 and IL13 serum concentrations, two cytokines belonging to the Th1 and Th2 profile respectively and biologically related to IL18.

METHODS

Ten patients with RA not responding to disease modifying antirheumatic drugs (DMARDs) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks. Serum samples were collected from all patients before each infusion and assayed for IL18, IL12, and IL13 by enzyme linked immunosorbent assay (ELISA); IL18 was also measured eight weeks after the last infusion.

RESULTS

Serum concentrations of IL18 in all patients were already markedly reduced from baseline after two weeks (p<0.005). Serum IL18 was also decreased in a stable manner after six (p<0.01) and 14 weeks (p<0.01) compared with baseline concentrations. No significant modifications were found in serum concentrations of IL12 and IL13 at any time point.

CONCLUSION

There was a rapid and persistent decrease in serum concentrations of IL18 in all the patients studied. This result provides evidence of an in vivo regulation of IL18 by TNFalpha and suggests that anti-TNFalpha therapy is likely to interrupt the synergistic effect between these two cytokines.

摘要

目的

测定接受英夫利昔单抗治疗(肿瘤坏死因子(TNF)α阻断)的类风湿关节炎(RA)患者血清白细胞介素(IL)-18浓度,并评估同时发生的IL-12和IL-13血清浓度变化,这两种细胞因子分别属于Th1和Th2细胞因子谱,且在生物学上与IL-18相关。

方法

10例对改善病情抗风湿药(DMARDs)无反应的RA患者在基线时、2周后和6周后接受静脉注射英夫利昔单抗,剂量为3mg/kg。在每次输注前采集所有患者的血清样本,采用酶联免疫吸附测定(ELISA)法检测IL-18、IL-12和IL-13;在最后一次输注后8周也检测IL-18。

结果

所有患者血清IL-18浓度在2周后已较基线显著降低(p<0.005)。与基线浓度相比,6周(p<0.01)和14周(p<0.01)后血清IL-18也以稳定的方式降低。在任何时间点,IL-12和IL-13的血清浓度均未发现显著变化。

结论

在所有研究患者中,血清IL-18浓度迅速且持续下降。这一结果提供了TNFα对IL-18进行体内调节的证据,并表明抗TNFα治疗可能会中断这两种细胞因子之间的协同效应。

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