Serum cytokines of patients with migraine during attacks and attacks-free periods

2.ABSTRACTSERUM CYTOKINE LEVELS OF PATIENTS WITH MIGRAINE DURINGATTACKS AND ATTACK-FREE PERIODSMigraine is a highly prevalent neurovascular disorder that affects a significantproportion of the adult population worldwide; it represents an enormous socio-economic burden to the individual as well as to the society and affects the quality oflife. The molecular mechanisms of migraine have not yet been fully clarified and themechanisms leading to the typical headache in migraine are still not understood. Ingeneral, headache is mediated through the trigeminal nociceptive fibres of dural andmeningeal vessels and meninges. A centrally triggered neurovascular inflammationwith isolated release of nonalgesic CGRP, which is documented for humans during amigraine attack, would also not account for the painful sensation. Thus, thehypothesis of cytokines as possible pain mediators in neurovascular inflammationoffers a potential mechanism for the generation of migraine pain. Cytokines havebeen shown to induce headache, but few studies examined cytokine levels inmigraine patients. The aim of this study was to determine the levels of TNF-α, IL-4,IL-5, IL-6, IL-10, and IFN- γ in serum of patients with migraine during attacks andattack-free periods.We evalueted 70 patients with migraine: 15 with aura and 20 without aura.Patients ranged in age from 17 to 55 (mean, 37 years), and the male-to-female ratiowas 3:7. 19 healthy people without any diagnosis of migraine or headache were usedas a control group. The control group had the same mean age and sex ratio as thepatients. A detailed history was taken and a thorough physical examination wasperformed. The diagnosis of migraine was based on the criteria of ICHD-II (2004) .Exclution criteria included prophylactic therapy in the last 3 months; previous historyof chronic liver disease, chronic renal failure, or hematologic or autoimmune disease;infectious disease; diarrhea; pregnancy and previous history of severe systemicdisease or systemic hypertension. Blood was drawn from the antecubital vein,centrifuged, and stored at -80oC until analyzed. Levels of TNF-α, IL-4, IL-5, IL-6,IL-10, and IFN- γ in plasma samples were determined by enzyme-linkedimmunosorbent assay (ELISA) techniques. The statistical assesment was conducted.TNF-α levels in migraine patients were significantly higher than in healthycontrols. A significant change in serum TNF-α levels in patients with migraine withaura during migraine attacks. The levels of IL-6 high in all migraine subgroupscompared to controls. In attack groups, IL-10 levels were found higher than inattack-free groups and healthy controls (p<0.05). No significant change in plasma IL-4 and IL-5 levels in patients with migraine compared to controls was observed. Nodifferences were detected in IFN- γ levels between the groups.A neuroimmune mechanism for migraine was tested with expected increasesin some cytokines tested during a migraine. Changes of the level of TNF-α, IL-6 andIL-10 in the blood of patients with migraine may suggest that neurogenicinflammation participates in the pathogenesis of migraine. A better understanding ofthe role cytokines in migraine will enhance knowledge of specific neurobiologicalmechanisms in health and disease and provide opportunities for novel treatmentinterventions. Any differences noted would expand and clarify a neuroimmunehypothesis of migraine pathogenesis and lead to future diagnostic markers ortherapeutic options or both for the disorder.Key-words: Cytokines; migraine