{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:51:35Z","timestamp":1787010695749,"version":"build-2736575974"},"posted":{"date-parts":[[2023,1,13]]},"group-title":"Neuroscience","reference-count":91,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,1,14]]},"abstract":"<jats:p>\n                  Interleukin-6 (IL-6) has been long considered a key player in cancer-associated cachexia\n                  <jats:sup>1-15<\/jats:sup>\n                  . It is believed that sustained elevation of IL-6 production during cancer progression causes brain dysfunctions, which ultimately result in cachexia\n                  <jats:sup>16-20<\/jats:sup>\n                  . However, how peripheral IL-6 influences the brain remains poorly understood. Here we show that neurons in the area postrema (AP), a circumventricular structure in the hindbrain, mediate the function of IL-6 in cancer-associated cachexia in mice. We found that circulating IL-6 can rapidly enter the AP and activate AP neurons. Peripheral tumor, known to increase circulating IL-6\n                  <jats:sup>1-5,15,18,21-23<\/jats:sup>\n                  , leads to elevated IL-6 and neuronal hyperactivity in the AP, and causes potentiated excitatory synaptic transmission onto AP neurons. Remarkably, neutralization of IL-6 in the brain of tumor-bearing mice with an IL-6 antibody prevents cachexia, reduces the hyperactivity in an AP network, and markedly prolongs lifespan. Furthermore, suppression of\n                  <jats:italic>Il6ra<\/jats:italic>\n                  , the gene encoding IL-6 receptor, specifically in AP neurons with CRISPR\/dCas9 interference achieves similar effects. Silencing of Gfral-expressing AP neurons also ameliorates the cancer-associated cachectic phenotypes and AP network hyperactivity. Our study identifies a central mechanism underlying the function of peripheral IL-6, which may serve as a target for treating cancer-associated cachexia.\n                <\/jats:p>","DOI":"10.1101\/2023.01.12.523716","type":"posted-content","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T19:10:11Z","timestamp":1673637011000},"source":"Crossref","is-referenced-by-count":1,"title":["Area postrema neurons mediate interleukin-6 function in cancer-associated cachexia"],"prefix":"10.64898","author":[{"given":"Qingtao","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblle","family":"van de 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