{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T15:12:37Z","timestamp":1761491557701,"version":"3.41.2"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":106,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Karolinska Institutet and the Swedish Research Council","award":["2015-03028"],"award-info":[{"award-number":["2015-03028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Myalgic encephalomyelitis (ME) previously also known as chronic fatigue syndrome is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here, we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation targeting nerve endings in the nasal cavity, likely from the trigeminal nerve, possibly activating additional centers in the brainstem of ME patients and correlating with a \u223c30% reduction in overall symptom scores after 8 weeks of treatment. By performing longitudinal, systems-level monitoring of the blood immune system in these patients, we uncover signs of chronic immune activation in ME, as well as immunological correlates of improvement that center around gut-homing immune cells and reduced inflammation. The mechanisms of symptom relief remain to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We believe that these results are suggestive of ME as a condition explained by a maladaptive disease tolerance response following infection.<\/jats:p>","DOI":"10.1093\/oxfimm\/iqad003","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T14:29:50Z","timestamp":1681741790000},"source":"Crossref","is-referenced-by-count":3,"title":["Achieving symptom relief in patients with myalgic encephalomyelitis by targeting the neuro-immune interface and optimizing disease tolerance"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3692-9060","authenticated-orcid":false,"given":"Lucie","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health , Karolinska Institutet , Solna 17121, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Pou","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health , Karolinska Institutet , Solna 17121, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadepally","family":"Lakshmikanth","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health , Karolinska Institutet , Solna 17121, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5685-8386","authenticated-orcid":false,"given":"Jingdian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics , Karolinska Institutet , Solna 17176, Sweden"},{"name":"Max Planck Institute Biology of Ageing\u2014Karolinska Institutet Laboratory , Karolinska Institutet , Solna 17176, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantin Habimana","family":"Mugabo","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health , Karolinska Institutet , Solna 17121, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health , Karolinska Institutet , Solna 17121, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaromir","family":"Mikes","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health , Karolinska Institutet , Solna 17121, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Olin","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health , Karolinska Institutet , Solna 17121, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9323-5751","authenticated-orcid":false,"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health , Karolinska Institutet , Solna 17121, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2891-2840","authenticated-orcid":false,"given":"Joanna","family":"Rorbach","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics , Karolinska Institutet , Solna 17176, Sweden"},{"name":"Max Planck Institute Biology of Ageing\u2014Karolinska Institutet Laboratory , Karolinska Institutet , Solna 17176, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Erik","family":"Juto","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Intervention and Technology , Karolinska Institutet , Solna 17177, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tie Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Intervention and Technology , Karolinska Institutet , Solna 17177, Sweden"},{"name":"Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital , Solna 17176, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Julin","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Care Sciences and Society , Karolinska Institutet , Solna 17176, Sweden"},{"name":"Neurological Rehabilitation Clinic, Stora Sk\u00f6ndal , Sk\u00f6ndal 12864, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8103-0046","authenticated-orcid":false,"given":"Petter","family":"Brodin","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health , Karolinska Institutet , Solna 17121, Sweden"},{"name":"Department of Immunology and Inflammation, Imperial College London , London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"2023042920052681800_iqad003-B1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1001\/jama.2019.8312","article-title":"Advances in understanding the pathophysiology of chronic fatigue syndrome","volume":"322","author":"Komaroff","year":"2019","journal-title":"JAMA"},{"key":"2023042920052681800_iqad003-B2","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1001\/jama.2015.1346","article-title":"Beyond myalgic encephalomyelitis\/chronic fatigue syndrome: An IOM report on redefining an illness","volume":"313","author":"Clayton","year":"2015","journal-title":"JAMA"},{"key":"2023042920052681800_iqad003-B3","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1515\/reveh-2015-0026","article-title":"Review of myalgic encephalomyelitis\/chronic fatigue syndrome: An evidence-based approach to diagnosis and management by 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