Proinflammatory Cytokines, Adhesion Molecules, and Lymphocyte Integrin Expression in the Internal Jugular Blood of Migraine Patients Without Aura Assessed Ictally


  • Paola Sarchielli MD,

  • Andrea Alberti MD,

  • Antonio Baldi MD,

  • Francesca Coppola MD,

  • Cristiana Rossi MD,

  • Laura Pierguidi MD,

  • Alessandro Floridi PhD,

  • Paolo Calabresi MD

  • From the Neurologic Clinic, Department of Medical Specialties and Public Health, University of Perugia, Italy (Drs. Sarchielli, Alberti, Baldi, Coppola, Rossi, Pierguidi, Floridi, and Calabresi).

Address all correspondence to Paola Sarchielli, Neurologic Clinic, Ospedale Silvestrini, 06156 Perugia, Italy.


Objective.—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-α[TNF-α], interleukin-1β[IL-1β], IL-4, and IL-6) were also determined and correlated with those of adhesion molecules.

Patients and Methods.—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.

Results.—A parallel transient increase of sICAM-1, TNF-α, 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.

Conclusions.—The transient increase in sICAM-1 and TNF-α 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.