Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally

Headache. 2006 Feb;46(2):200-7. doi: 10.1111/j.1526-4610.2006.00337.x.

Abstract

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-alpha[TNF-alpha], interleukin-1beta[IL-1beta], 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-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.

Conclusions: 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.

MeSH terms

  • Cytokines / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Integrin alpha4beta1 / blood
  • Integrins / blood*
  • Intercellular Adhesion Molecule-1 / blood*
  • Interleukin-1 / blood
  • Interleukin-4 / blood
  • Interleukin-6 / blood
  • Jugular Veins
  • Lymphocyte Function-Associated Antigen-1 / blood
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Migraine without Aura / blood*
  • Time Factors
  • Tumor Necrosis Factor-alpha / analysis
  • Vascular Cell Adhesion Molecule-1 / blood*

Substances

  • Cytokines
  • Integrin alpha4beta1
  • Integrins
  • Interleukin-1
  • Interleukin-6
  • Lymphocyte Function-Associated Antigen-1
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Interleukin-4