Sega Sasa, Horvat Alenka, Rot Uros, Wraber Branka, Ihan Alojz
Department of Neurology, University Clinical Centre Ljubljana, Ljubljana, Slovenia.
Clin Neurol Neurosurg. 2008 Nov;110(9):947-50. doi: 10.1016/j.clineuro.2008.02.020. Epub 2008 Apr 8.
Some patients with relapsing-remitting multiple sclerosis (RRMS) do not respond to treatment with interferon-beta and continue to have relapses and new enhancing lesions on MRI. The markers which would predict the treatment response are still not known. The objectives of the study were to compare cytokines levels (IFN-gamma, IL-4, IL-6, IL-10) and expression of adhesion molecules before and during treatment in responders and nonresponders to IFN-beta treatment.
Twenty-nine patients with RRMS were enrolled in the study. Cytokine levels were evaluated by ELISA in supernatants of IONO/PMA activated PBMC cultures (IFN-gamma, IL-4, IL-6, IL-10), and by flow cytometry (intracellular IFN-gamma, IL-4 and IL-2R expression) before and during treatment. Expression of adhesion molecules (VLA-4, ICAM-1) was evaluated by flow cytometry (CD49+ and CD54+) before and during treatment.
Only 9 of 29 patients were responders to treatment according to definition (no relapse in the first 2 years of treatment). We found significant differences in the expression of IL-2R after 1 month of treatment, intracellular IFN-gamma after 6 months of treatment and IL-10 level in nonactivated PBMC cultures after 1 week of treatment.
We concluded that the differences we had found between responders and nonresponders are most probably incidental and not predictive of treatment response. Our study shows that cytokines levels and expression of adhesion molecules cannot be used as markers for treatment response.
一些复发缓解型多发性硬化症(RRMS)患者对β-干扰素治疗无反应,且在MRI上持续出现复发和新的强化病灶。目前仍不清楚哪些标志物可预测治疗反应。本研究的目的是比较对β-干扰素治疗有反应者和无反应者在治疗前及治疗期间的细胞因子水平(干扰素-γ、白细胞介素-4、白细胞介素-6、白细胞介素-10)和黏附分子表达。
29例RRMS患者纳入本研究。通过ELISA法检测离子霉素/佛波醇酯(IONO/PMA)激活的外周血单个核细胞(PBMC)培养上清液中的细胞因子水平(干扰素-γ、白细胞介素-4、白细胞介素-6、白细胞介素-10),并在治疗前及治疗期间通过流式细胞术检测细胞内干扰素-γ、白细胞介素-4和白细胞介素-2受体表达。通过流式细胞术(CD49+和CD54+)检测治疗前及治疗期间黏附分子(VLA-4、ICAM-1)的表达。
根据定义,29例患者中只有9例对治疗有反应(治疗的前2年无复发)。我们发现治疗1个月后白细胞介素-2受体表达、治疗6个月后细胞内干扰素-γ以及治疗1周后未激活的PBMC培养物中白细胞介素-10水平存在显著差异。
我们得出结论,有反应者和无反应者之间的差异很可能是偶然的,并非治疗反应的预测指标。我们的研究表明,细胞因子水平和黏附分子表达不能用作治疗反应的标志物。