Sarchielli Paola, Alberti Andrea, Baldi Antonio, Coppola Francesca, Rossi Cristiana, Pierguidi Laura, Floridi Alessandro, Calabresi Paolo
Neurologic Clinic, Department of Medical Specialties and Public Health, University of Perugia, Italy.
Headache. 2006 Feb;46(2):200-7. doi: 10.1111/j.1526-4610.2006.00337.x.
The aim of the present research was to verify the levels of the soluble adhesion molecules sL- and sE-selectins, intercellular adhesion molecule (sICAM)-1, and vascular cell adhesion molecule-1 in serial samples of internal jugular venous blood taken from migraine patients without aura (MWoA) during attacks. The expression of leukocyte function antigen (LFA)-1 and very late activation antigen (VLA)-4 was also assessed on lymphocytes obtained from jugular venous blood. Levels of certain proinflammatory cytokines (tumor necrosis factor-alpha[TNF-alpha], interleukin-1beta[IL-1beta], IL-4, and IL-6) were also determined and correlated with those of adhesion molecules.
Seven MWoA patients were admitted in the hospital during attacks and blood samples were taken immediately after catheter insertion, at 1, 2, and 4 hours after attack onset, and within 2 hours after its termination. The levels of adhesion molecules and cytokines were measured with ELISA method. The expression of LFA-1 and VLA-4 was assessed by flow cytometry.
A parallel transient increase of sICAM-1, TNF-alpha, and IL-6 was observed in the first 2 hours after attack onset compared with the time of catheter insertion (P < .0001, <.001, and <.003, respectively). The proportion of CD4+ and CD8+ T-cells expressing high levels of LFA-1 showed instead a progressive down-regulation with significantly lower percentages at 2 and 4 hours after attack onset (P < .01 and <.022, respectively). No variation in the percentage of VLA-4 expressing cells was observed at any time of the study.
The transient increase in sICAM-1 and TNF-alpha found in the internal jugular blood of MWoA patients assessed ictally can be induced by sensory neuropeptides released from activated trigeminal endings. The progressive decrease in sICAM-1 levels during attacks and the down-regulation of LFA-1 expression by lymphocytes could antagonize their transvascular migration, supporting the hypothesis of sterile inflammation in the dura mater during migraine attacks.
本研究旨在验证无先兆偏头痛（MWoA）患者发作期间颈内静脉血系列样本中可溶性黏附分子sL-和sE-选择素、细胞间黏附分子（sICAM）-1和血管细胞黏附分子-1的水平。还评估了从颈静脉血中获取的淋巴细胞上白细胞功能抗原（LFA）-1和极晚期活化抗原（VLA）-4的表达。还测定了某些促炎细胞因子（肿瘤坏死因子-α[TNF-α]、白细胞介素-1β[IL-1β]、IL-4和IL-6）的水平，并将其与黏附分子的水平进行关联。
7例MWoA患者在发作期间入院，在插入导管后立即、发作开始后1小时、2小时和4小时以及发作终止后2小时内采集血样。采用酶联免疫吸附测定（ELISA）法测量黏附分子和细胞因子的水平。通过流式细胞术评估LFA-1和VLA-4的表达。
与插入导管时相比，发作开始后的前2小时观察到sICAM-1、TNF-α和IL-6平行短暂升高（分别为P <.0001、<.001和<.003）。相反，表达高水平LFA-1的CD4 +和CD8 + T细胞比例呈逐渐下调，发作开始后2小时和4小时的百分比显著降低（分别为P <.01和<.022）。在研究的任何时间均未观察到表达VLA-4的细胞百分比有变化。
发作期评估的MWoA患者颈内静脉血中sICAM-1和TNF-α的短暂升高可能由活化三叉神经末梢释放的感觉神经肽诱导。发作期间sICAM-1水平的逐渐降低以及淋巴细胞对LFA-1表达的下调可能拮抗其跨血管迁移，支持偏头痛发作期间硬脑膜无菌性炎症的假说。
