INHIBITION OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1), SOLUBLE ICAM-1 AND INTERLEUKIN-4 BY NITRIC-OXIDE EXPRESSION IN MIGRAINE PATIENTS

The mechanisms of the postulated ''sterile'' inflammation in migraine were studied utilizing flow cytometry (intercellular adhesion molecule 1, ICAM-1; interleukin-1 receptor, IL-1R) and enzyme-linked immunosor bent assay (soluble intercellular adhesion molecule 1, sICAM-1; interl eukin-4, IL-4). Twenty patients suffering from migraine without aura, 20 healthy subjects, and 10 patients suffering from episodic tension h eadache were selected. All of the migraine patients were studied durin g a migraine crisis experimentally induced by the administration of is osorbide dinitrate (a nitric oxide donor), and 10 out the 20 were also studied during a spontaneous migraine attack. A sharp decrease in the expression of ICAM-1 (F=5.09, p<0.001 and F=2.46, p<0.05, respectivel y), sICAM-1 1 (F=6.21, p<0.0001 and F=3.99, p<0.007, respectively) and serum IL-4 (F=6.23, p<0.001 and F=3.64, p<0.01, respectively) were ob served in experimentally induced and spontaneous migraine attacks. The re was no change with respect to IL-IR 1 receptor expression values. T he two control groups, tested with the same experimental procedure, sh owed no changes in ICAM-1 and IL-1R or in in sICAM-1 and IL-4. Our dat a suggest that migraine patients are more sensitive to exogenous NO th an controls. In addition, our results indicate that experimental migra ine crisis, induced by an NO donor, is mediated by the inhibition of I L-4 and subsequently of ICAM-1. It is likely that the described ICAM-1 downregulation inhibits during a migraine attack the critical step of transendothelial migration into the cerebral tissues of activated leu kocytes, as proposed in the ''sterile inflammation'' hypothesis.