{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:46:41Z","timestamp":1789390001988,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this both narrative and systematic review, we explore the role of TNF-\u03b1 in the immunopathogenesis of Beh\u00e7et\u2019s disease (BD) and the effect of treatment with TNF-\u03b1 blockers. BD is an auto-inflammatory disease, characterized by recurrent painful oral ulcerations. The pathogenesis of BD is not yet elucidated; it is assumed that TNF-\u03b1 may play a key role. In the narrative review, we report an increased production of TNF-\u03b1, which may be stimulated via TLR-signaling, or triggered by increased levels of IL-1\u03b2 and IFN-\u03b3. The abundance of TNF-\u03b1 is found in both serum and in sites of inflammation. This increased presence of TNF-\u03b1 stimulates T-cell development toward pro-inflammatory subsets, such as Th17 and Th22 cells. Treatment directed against the surplus of TNF-\u03b1 is investigated in the systematic review, performed according to the PRISMA guideline. We searched the Pubmed and Cochrane database, including comparative studies only. After including 11 studies, we report a beneficial effect of treatment with TNF-\u03b1 blockers on the various manifestations of BD. In conclusion, the pivotal role of TNF-\u03b1 in the immunopathogenesis of BD is reflected in both the evidence of their pro-inflammatory effects in BD and in the evidence of the positive effect of treatment on the course of disease in BD.<\/jats:p>","DOI":"10.3390\/ijms21093072","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T05:05:32Z","timestamp":1588050332000},"page":"3072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Beh\u04abet\u2019s Disease, and the Role of TNF-\u03b1 and TNF-\u03b1 Blockers"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5896-7033","authenticated-orcid":false,"given":"Tim","family":"van der Houwen","sequence":"first","affiliation":[{"name":"Section of Clinical Immunology, Departments of Internal Medicine and Immunology, ErasmusMC, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"van Laar","sequence":"additional","affiliation":[{"name":"Section of Clinical Immunology, Departments of Internal Medicine and Immunology, ErasmusMC, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1056\/NEJM199910213411707","article-title":"Beh\u00e7et\u2019s Disease","volume":"341","author":"Sakane","year":"1999","journal-title":"N. 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