{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:33:55Z","timestamp":1792020835922,"version":"4.4.0"},"reference-count":34,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/01126"],"award-info":[{"award-number":["PI20\/01126"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Consejeria de Salud y Familias, Andalucia, Spain","award":["PE-0356-2018"],"award-info":[{"award-number":["PE-0356-2018"]}]},{"name":"Consejeria de Salud y Familias, Andalucia, Spain","award":["PI-0027-2020"],"award-info":[{"award-number":["PI-0027-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profiles in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early-onset MD (EOMD, &lt;35 years old), and 39 with late-onset MD (LOMD, &gt;50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL,1 and IL-1\u03b2 were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1\u03b2 were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p = 0.004) and a higher prevalence of migraine than LOMD (p = 0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3, and CXCL4 were different between patients with MD or migraine and controls.<\/jats:p>","DOI":"10.3390\/jcm10184052","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T02:41:07Z","timestamp":1631068867000},"page":"4052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Clinical and Cytokine Profile in Patients with Early and Late Onset Meniere Disease"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1816-9336","authenticated-orcid":false,"given":"Maria-Del-Carmen","family":"Moleon","sequence":"first","affiliation":[{"name":"Otology and Neurotology Group CTS495, Department of Genomic Medicine, GENYO\u2014Centre for Genomics and Oncological Research\u2014Pfizer\/University of Granada\/Junta de Andaluc\u00eda, PTS, 18016 Granada, Spain"},{"name":"Department of Otolaryngology, Instituto de Investigaci\u00f3n Biosanitaria ibs.Granada, Hospital Universitario Virgen de las Nieves, Universidad de Granada, 18014 Granada, Spain"},{"name":"Sensorineural Pathology Programme, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras, CIBERER, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6326-9021","authenticated-orcid":false,"given":"Estrella","family":"Martinez-Gomez","sequence":"additional","affiliation":[{"name":"Otology and Neurotology Group CTS495, Department of Genomic Medicine, GENYO\u2014Centre for Genomics and Oncological Research\u2014Pfizer\/University of Granada\/Junta de Andaluc\u00eda, PTS, 18016 Granada, Spain"},{"name":"Sensorineural Pathology Programme, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras, CIBERER, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2695-0739","authenticated-orcid":false,"given":"Marisa","family":"Flook","sequence":"additional","affiliation":[{"name":"Otology and Neurotology Group CTS495, Department of Genomic Medicine, GENYO\u2014Centre for Genomics and Oncological Research\u2014Pfizer\/University of Granada\/Junta de Andaluc\u00eda, PTS, 18016 Granada, Spain"},{"name":"Sensorineural Pathology Programme, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras, CIBERER, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreina","family":"Peralta-Leal","sequence":"additional","affiliation":[{"name":"Otology and Neurotology Group CTS495, Department of Genomic Medicine, GENYO\u2014Centre for Genomics and Oncological Research\u2014Pfizer\/University of Granada\/Junta de Andaluc\u00eda, PTS, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"Gallego","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Virgen de las Nieves, Universidad de Granada, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1273-0150","authenticated-orcid":false,"given":"Hortensia","family":"Sanchez-Gomez","sequence":"additional","affiliation":[{"name":"Otoneurology Unit, Department of Otorhinolaryngology, University Hospital of Salamanca, IBSAL, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alharilla","family":"Montilla-Iba\u00f1ez","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Complejo Hospitalario de Ja\u00e9n, 23007 Jaen, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Dominguez-Dur\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Hospital Virgen Macarena, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-329X","authenticated-orcid":false,"given":"Andres","family":"Soto-Varela","sequence":"additional","affiliation":[{"name":"Division of Neurotology, Department of Otorhinolaryngology, Complexo Hospitalario Universitario, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael","family":"Aran","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Complexo Hospitalario de Pontevedra, 36071 Pontevedra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6104-0941","authenticated-orcid":false,"given":"Lidia","family":"Frejo","sequence":"additional","affiliation":[{"name":"Otology and Neurotology Group CTS495, Department of Genomic Medicine, GENYO\u2014Centre for Genomics and Oncological Research\u2014Pfizer\/University of Granada\/Junta de Andaluc\u00eda, PTS, 18016 Granada, Spain"},{"name":"Sensorineural Pathology Programme, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras, CIBERER, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-1430","authenticated-orcid":false,"given":"Jose A.","family":"Lopez-Escamez","sequence":"additional","affiliation":[{"name":"Otology and Neurotology Group CTS495, Department of Genomic Medicine, GENYO\u2014Centre for Genomics and Oncological Research\u2014Pfizer\/University of Granada\/Junta de Andaluc\u00eda, PTS, 18016 Granada, Spain"},{"name":"Department of Otolaryngology, Instituto de Investigaci\u00f3n Biosanitaria ibs.Granada, Hospital Universitario Virgen de las Nieves, Universidad de Granada, 18014 Granada, Spain"},{"name":"Sensorineural Pathology Programme, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras, CIBERER, 28029 Madrid, Spain"},{"name":"Department of Surgery, Division of Otolaryngology, Facultad de Medicina, Universidad de Granada, 18006 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/head.13240","article-title":"Clinical Features, Familial History, and Migraine Precursors in Patients with Definite Vestibular Migraine: The VM-Phenotypes Projects","volume":"58","author":"Teggi","year":"2018","journal-title":"Headache J. Head Face Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.ncl.2015.04.008","article-title":"Early Diagnosis and Management of Acute Vertigo from Vestibular Migraine and M\u00e9ni\u00e8re\u2019s Disease","volume":"33","author":"Seemungal","year":"2015","journal-title":"Neurol. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/VES-150549","article-title":"Diagnostic criteria for Meni\u00e8re\u2019s disease","volume":"25","author":"Carey","year":"2015","journal-title":"J. Vestib. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3389\/fneur.2016.00182","article-title":"Clinical Subgroups in Bilateral Meniere Disease","volume":"7","author":"Frejo","year":"2016","journal-title":"Front. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1111\/coa.12844","article-title":"Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis","volume":"42","author":"Frejo","year":"2017","journal-title":"Clin. Otolaryngol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/cge.12150","article-title":"Familial clustering and genetic heterogeneity in Meniere\u2019s disease","volume":"85","author":"Requena","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1002\/lary.25207","article-title":"Genetic aspects and clinical characteristics of familial meniere\u2019s disease in a South Korean population","volume":"125","author":"Lee","year":"2015","journal-title":"Laryngoscope"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1097\/AUD.0000000000000878","article-title":"Burden of Rare Variants in the OTOG Gene in Familial Meniere\u2019s Disease","volume":"41","author":"Aran","year":"2020","journal-title":"Ear Hear."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5974","DOI":"10.1038\/s41598-018-23911-4","article-title":"Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease","volume":"8","author":"Frejo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.3389\/fimmu.2019.01229","article-title":"Differential Proinflammatory Signature in Vestibular Migraine and Meniere Disease","volume":"10","author":"Flook","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s40136-018-0182-8","article-title":"Meniere\u2019s Disease: Genetics and the Immune System","volume":"6","author":"Flook","year":"2018","journal-title":"Curr. Otorhinolaryngol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"Headache Classification Committee of the International Headache Society (IHS) the International Classification of Headache Disorders","volume":"38","author":"Arnold","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3233\/VES-2012-0453","article-title":"Vestibular migraine: Diagnostic criteria","volume":"22","author":"Lempert","year":"2012","journal-title":"J. Vestib. Res."},{"key":"ref_14","unstructured":"Moore, D.S., and McCabe, G.P. (2005). Introduction to the Practice of Statistics, W.H. Freeman & Company. [5th ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1007\/s00415-011-5999-8","article-title":"Pharmacotherapy of vestibular and ocular motor disorders, including nystagmus","volume":"258","author":"Strupp","year":"2011","journal-title":"J. Neurol."},{"key":"ref_16","first-page":"257","article-title":"Meni\u00e8re\u2019s disease","volume":"Volume 137","year":"2016","journal-title":"The Human Hypothalamus\u2014Neuroendocrine Disorders"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.autrev.2012.01.004","article-title":"Meniere\u2019s disease might be an autoimmune condition?","volume":"11","author":"Greco","year":"2012","journal-title":"Autoimmun. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e548","DOI":"10.1097\/MAO.0000000000002198","article-title":"Vestibular Aqueduct Morphology Correlates with Endolymphatic Sac Pathologies in Meni\u00e8re\u2019s Disease\u2014A Correlative Histology and Computed Tomography Study","volume":"40","author":"Luu","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_19","first-page":"82","article-title":"Enrichment of damaging missense variants in genes related with axonal guidance signalling in sporadic Meniere\u2019s disease","volume":"57","author":"Requena","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fgene.2019.00076","article-title":"Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease","volume":"10","author":"Requena","year":"2019","journal-title":"Front. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.4049\/jimmunol.1401138","article-title":"CXCL1 Contributes to Host Defense in Polymicrobial Sepsis via Modulating T Cell and Neutrophil Functions","volume":"193","author":"Jin","year":"2014","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33123","DOI":"10.1038\/srep33123","article-title":"Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions","volume":"6","author":"Sawant","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Atri, C., Guerfali, F.Z., and Laouini, D. (2018). Role of Human Macrophage Polarization in Inflammation during Infectious Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061801"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Scheu, S., Ali, S., Ruland, C., Arolt, V., and Alferink, J. (2017). The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112306"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1615\/CritRevImmunol.v22.i2.10","article-title":"Regulation of Macrophage-Derived Chemokine (MDC\/ CCL22) Production","volume":"22","author":"Yamashita","year":"2002","journal-title":"Crit. Rev. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/BF00453677","article-title":"Endolymphatic hydrops: Mechanical causes of hearing loss","volume":"212","author":"Tonndorf","year":"1976","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/lio2.28","article-title":"AAO: Autoimmune and Autoinflammatory (Disease) in Otology: What is New in Immune-Mediated Hearing Loss","volume":"1","author":"Vambutas","year":"2016","journal-title":"Laryngoscope"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1046\/j.1468-2982.2003.00453.x","article-title":"Decreased Stnf-Ri in Migraine Patients?","volume":"23","author":"Empl","year":"2003","journal-title":"Cephalalgia"},{"key":"ref_29","first-page":"1979","article-title":"Roles of claudin-5 and von Willebrand factor in patients with rheumatoid arthritis","volume":"8","author":"Gurol","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_30","first-page":"930","article-title":"Serum levels of endocan, claudin-5 and cytokines in mi-graine","volume":"20","author":"Kotan","year":"2016","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ejphar.2018.12.004","article-title":"Progression in migraine: Role of mast cells and pro-inflammatory and anti-inflammatory cytokines","volume":"844","author":"Conti","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jneuroim.2005.10.005","article-title":"The importance of cytokines, chemokines and nitric oxide in pathophysiology of migraine","volume":"171","author":"Fidan","year":"2006","journal-title":"J. Neuroimmunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jneuroim.2017.09.008","article-title":"Unbalanced plasma TNF-\u03b1 and IL-12\/IL-10 profile in women with migraine is associated with psychological and physiological outcomes","volume":"313","author":"Oliveira","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107872","DOI":"10.1016\/j.heares.2019.107872","article-title":"Genetic architecture of Meniere\u2019s disease","volume":"397","year":"2020","journal-title":"Hear. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/18\/4052\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:58:22Z","timestamp":1760165902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/18\/4052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,7]]},"references-count":34,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["jcm10184052"],"URL":"https:\/\/doi.org\/10.3390\/jcm10184052","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202108.0162.v1","asserted-by":"object"}]},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,7]]}}}