{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:54:24Z","timestamp":1789430064538,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T00:00:00Z","timestamp":1343347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The expression of proinflammatory factors such as tumor necrosis factor \u03b1 (TNF\u03b1), interleukin\u20106 (IL\u20106), IL\u20108, and prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) is significantly correlated with the symptoms of herniated disc disease. Among the different types of immune cells, macrophages are frequently noted in the herniated disc tissue. We undertook this study to clarify the interaction of the intervertebral disc (IVD) and macrophages with regard to the production of TNF\u03b1, IL\u20106, IL\u20108, and PGE<jats:sub>2<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We developed 2 animal models to assess the interactions of IVDs with macrophages in terms of TNF\u03b1, IL\u20106, IL\u20108, and PGE<jats:sub>2<\/jats:sub> production and pain\u2010related behavior. We also cocultured IVDs and macrophages to assess the role of TNF\u03b1 in IL\u20106, IL\u20108, and PGE<jats:sub>2<\/jats:sub> production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IVD autografts induced TNF\u03b1, IL\u20106, IL\u20108, and cyclooxygenase 2 (COX\u20102) messenger RNA (mRNA) up\u2010regulation; macrophage infiltration was seen shortly after the autograft was implanted. A significant decrease was noted in the mechanical threshold of the ipsilateral paw following the up\u2010regulation of TNF\u03b1, IL\u20106, IL\u20108, and COX\u20102 mRNA. Only IVD and macrophage cocultures resulted in IL\u20108 and PGE<jats:sub>2<\/jats:sub> up\u2010regulation. TNF\u03b1 up\u2010regulation was maximized before that of IL\u20106 and IL\u20108. TNF\u03b1 neutralization attenuated production of IL\u20106 and PGE<jats:sub>2<\/jats:sub>, but not that of IL\u20108. Neutralization of TNF\u03b1 and IL\u20108 significantly increased the paw withdrawal mechanical threshold in the IVD autograft and spinal nerve ligation model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IVD\u2013macrophage interaction plays a major role in sciatica and in the production of TNF\u03b1, IL\u20106, IL\u20108, and PGE<jats:sub>2<\/jats:sub>. TNF\u03b1 is required for IL\u20106 and PGE<jats:sub>2<\/jats:sub> production, but not for IL\u20108 production, during IVD\u2013macrophage interaction. Neutralization of TNF\u03b1 and IL\u20108 can be a valuable therapy for herniated disc disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34456","type":"journal-article","created":{"date-parts":[[2012,3,6]],"date-time":"2012-03-06T01:27:36Z","timestamp":1330997256000},"page":"2601-2610","source":"Crossref","is-referenced-by-count":69,"title":["Intervertebral disc and macrophage interaction induces mechanical hyperalgesia and cytokine production in a herniated disc model in rats"],"prefix":"10.1002","volume":"64","author":[{"given":"Toru","family":"Takada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Nishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Maeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Kakutani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yurube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Doita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Kurosaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,7,27]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199612151-00005"},{"key":"e_1_2_7_3_2","unstructured":"Ministry of Health Labour and Welfare Japan. 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