The role of cytokines in migraine: A systematic review

Abstract

Background Cytokines are important endogenous substances that are involved in immune and inflammatory responses. Neurogenic inflammation has been proposed to play a role in migraine involving altered cytokine levels. Therefore, we aimed to provide a systematic review on the current knowledge on cytokine levels in migraine patients during and outside attacks. Methods Databases of PubMed and Embase were systematically searched for studies investigating cytokine levels in migraine patients during and outside attacks. Results Screening yielded identification of 45 articles investigating 18 cytokines in total. We found that the interictal level of the anti-inflammatory cytokine, interleukin 10, was decreased, while the level of transforming growth factor beta 1 was increased in migraine patients compared to controls. Levels of pro-inflammatory cytokines, tumor necrosis factor α and interleukin 6, were increased outside attacks compared to controls. Ictal levels of cytokines were unchanged or varying compared to the interictal state in migraine patients. Three studies reported dynamic cytokines levels during the course of an attack. Conclusion The findings of the current review underline a possible involvement of cytokines in the proposed inflammatory mechanisms of migraine. However, future studies are needed to expand our knowledge of the exact role of cytokines in the migraine pathophysiology with focus on cytokines TNF-α, IL-1ß, IL-6 and IL-10 while applying refined methodology.

Lack of Association between Common LAG3/CD4 Variants and Risk of Migraine

“…The probable role of inflammatory factors in the pathogenesis of migraine has been suggested, at least, by the following data: Description of the possible involvement of cytokines in the proposed inflammatory mechanisms of migraine [ 11 ], suggested by the increased serum levels of pro-inflammatory cytokines (tumor necrosis factor α -TNF-α-, interleukin 6- IL-6-, and IL-1β), and transforming growth factor beta 1 (TGF1β), and decreased serum levels of the anti-inflammatory cytokine IL-10 [ 12 , 13 ], compared with controls. TNF-α is increased in the cerebrospinal fluid of patients with chronic migraine as well [ 14 ].…”

What is the efficacy of aerobic exercise versus strength training in the treatment of migraine? A systematic review and network meta-analysis of clinical trials

“…Thus, the intensity-specific clinical benefit of aerobic exercise in migraine could be influenced by patients' endogenous opioidergic/endocannabinoidergic profile. Furthermore, the multifactorial pathophysiology of migraine may involve abnormal musculoskeletal/brain energy metabolism and mitochondrial disfunction [59], and inflammation [60,61]. This apparent dose-dependent effect of aerobic exercise on migraine could be mediated by improved mitochondrial/cardiorespiratory function [17], as well as by anti-inflammatory mechanisms associated with aerobic exercise [26,62].…”

Biomarkers of Migraine: An Integrated Evaluation of Preclinical and Clinical Findings

“…Although there may be some differences, it is clear that changes in inflammatory cytokines play a role in migraine. The findings related to cytokine changes in migraine have been the object of recent overviews [ 130 , 131 ]. Similarly, the C-reactive protein (CRP), a positive acute-phase protein that increases in response to inflammation, might play a role in migraine pathogenesis, but the findings are conflicting [ 132 , 133 , 134 , 135 ].…”

“…Similarly, the C-reactive protein (CRP), a positive acute-phase protein that increases in response to inflammation, might play a role in migraine pathogenesis, but the findings are conflicting [ 132 , 133 , 134 , 135 ]. In this section, we focus on the serum/plasma or CSF levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) because of their crucial role in trigeminal pain [ 130 , 136 , 137 ].…”

“…For instance, anticoagulants or specific clock proteins in the circadian system may interfere with assays [ 143 ]. Some studies suggest that the serum levels of IL-6 and TNF-α are higher in CM patients than in EM patients [ 130 , 134 , 144 ], although Rozen and Swidan described a substantial rise in TNF-α levels in the CSF, but not serum, of CM patients when compared to HC [ 145 ].…”