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 sa...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 IL6) 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-αfound 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.展开更多
Objective. - To investigate changes in the levels of calcitonin gene- related peptide and its intracellular messenger cyclic adenosine monophosphate in serial samples of internal jugular blood taken from migraine pati...Objective. - To investigate changes in the levels of calcitonin gene- related peptide and its intracellular messenger cyclic adenosine monophosphate in serial samples of internal jugular blood taken from migraine patients without aura assessed during attacks, and to assess their relationship with the levels of IL- 8, MCP- 1, and RANTES in the same samples. Background. - Calcitonin gene- related peptide, the marker of trigeminovascular activation, is released in both the internal and external jugular venous blood of migraine patients during attacks. Experimental evidence demonstrated that when released from C- type sensory neurons in inflammatory pain models, it differentially induced expression of neutrophil chemotactic chemokine IL- 8, but not monocyte chemotactic chemokine MCP- 1 or lymphocyte chemotactic chemokine RANTES. These chemokines were never investigated in migraine. Design/Methods. - Eight migraine without aura patients were admitted to the hospital during the attacks. Internal jugular venous blood samples were taken immediately after catheter insertion, at the 1st, 2nd, and 4th hours after attack onset, and within 2 hours from its cessation. The levels of the sensory neuropeptide calcitonin gene- related peptide and the messenger cyclic adenosine monophosphate were measured by RIA method, and those of IL- 8, MCP- 1,and RANTES were measured by ELISA method. Results. - Higher calcitonin gene- related peptide levels were found in the internal jugular venous blood of migraine without aura patients compared with the time of catheter insertion (ANOVA: P < .0001) with a peak at the first hour (52.6 ± 9.2 ng/mL). A transient increase in IL- 8 was observed at the 2nd and 4th hours (P < .01 and P < .002, respectively), whereas no changes in the levels of MCP- 1 and RANTES were found at any time of the study. The increase in IL- 8 was accompanied by a parallel increase in cyclic adenosine monophosphate. Conclusions. - The present study confirms previous findings of an increase in calcitonin gene- related peptide in internal jugular venousblood of migraine without aura patients during attacks. The transient increase in the levels of IL- 8 concurs with the results of recent experimental research showing a calcitonin gene- related peptide- induced activation of IL- 8 gene expression, but not RANTES and MCP- 1, via the transcriptional factor AP- 2, which mediates transduction in response to cyclic adenosine monophosphate. Although IL- 8 is transiently increased during migraine attacks, an accumulation of leukocytes secondary to neurogenic inflammation is unlikely, as it is for other inflammatory events, because they are self limiting. Other events, including nitric oxide production, may contribute to counteract meningeal transvascular leukocyte migration during migraine attacks, as suggested by the model of sterile inflammation.展开更多
文摘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 IL6) 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-αfound 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.
文摘Objective. - To investigate changes in the levels of calcitonin gene- related peptide and its intracellular messenger cyclic adenosine monophosphate in serial samples of internal jugular blood taken from migraine patients without aura assessed during attacks, and to assess their relationship with the levels of IL- 8, MCP- 1, and RANTES in the same samples. Background. - Calcitonin gene- related peptide, the marker of trigeminovascular activation, is released in both the internal and external jugular venous blood of migraine patients during attacks. Experimental evidence demonstrated that when released from C- type sensory neurons in inflammatory pain models, it differentially induced expression of neutrophil chemotactic chemokine IL- 8, but not monocyte chemotactic chemokine MCP- 1 or lymphocyte chemotactic chemokine RANTES. These chemokines were never investigated in migraine. Design/Methods. - Eight migraine without aura patients were admitted to the hospital during the attacks. Internal jugular venous blood samples were taken immediately after catheter insertion, at the 1st, 2nd, and 4th hours after attack onset, and within 2 hours from its cessation. The levels of the sensory neuropeptide calcitonin gene- related peptide and the messenger cyclic adenosine monophosphate were measured by RIA method, and those of IL- 8, MCP- 1,and RANTES were measured by ELISA method. Results. - Higher calcitonin gene- related peptide levels were found in the internal jugular venous blood of migraine without aura patients compared with the time of catheter insertion (ANOVA: P < .0001) with a peak at the first hour (52.6 ± 9.2 ng/mL). A transient increase in IL- 8 was observed at the 2nd and 4th hours (P < .01 and P < .002, respectively), whereas no changes in the levels of MCP- 1 and RANTES were found at any time of the study. The increase in IL- 8 was accompanied by a parallel increase in cyclic adenosine monophosphate. Conclusions. - The present study confirms previous findings of an increase in calcitonin gene- related peptide in internal jugular venousblood of migraine without aura patients during attacks. The transient increase in the levels of IL- 8 concurs with the results of recent experimental research showing a calcitonin gene- related peptide- induced activation of IL- 8 gene expression, but not RANTES and MCP- 1, via the transcriptional factor AP- 2, which mediates transduction in response to cyclic adenosine monophosphate. Although IL- 8 is transiently increased during migraine attacks, an accumulation of leukocytes secondary to neurogenic inflammation is unlikely, as it is for other inflammatory events, because they are self limiting. Other events, including nitric oxide production, may contribute to counteract meningeal transvascular leukocyte migration during migraine attacks, as suggested by the model of sterile inflammation.
