{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:26:40Z","timestamp":1792099600358,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T00:00:00Z","timestamp":1548288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007472","name":"University of Kentucky","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007472","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Azithromycin (AZM) and other macrolide antibiotics are applied as immunomodulatory treatments for CNS disorders. The immunomodulatory and antibiotic properties of AZM are purportedly independent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To improve the efficacy and reduce antibiotic resistance risk of AZM\u2010based therapies, we evaluated the immunomodulatory and neuroprotective properties of novel AZM derivatives. We semisynthetically prepared derivatives by altering sugar moieties established as important for inhibiting bacterial protein synthesis. Bone marrow\u2010derived macrophages (BMDMs) were stimulated in vitro with proinflammatory, M1, stimuli (LPS + INF\u2010gamma) with and without derivative costimulation. Pro\u2010 and anti\u2010inflammatory cytokine production, IL\u201012 and IL\u201010, respectively, was quantified using ELISA. Neuron culture treatment with BMDM supernatant was used to assess derivative neuroprotective potential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Azithromycin and some derivatives increased IL\u201010 and reduced IL\u201012 production of M1 macrophages. IL\u201010\/IL\u201012 cytokine shifts closely correlated with the ability of AZM and derivatives to mitigate macrophage neurotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Sugar moieties that bind bacterial ribosomal complexes can be modified in a manner that retains AZM immunomodulation and neuroprotection. Since the effects of BMDMs in vitro are predictive of CNS macrophage responses, our results open new therapeutic avenues for managing maladaptive CNS inflammation and support utilization of IL\u201010\/12 cytokine profiles as indicators of macrophage polarization and neurotoxicity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13092","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T22:57:35Z","timestamp":1548370655000},"page":"591-600","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Macrolide derivatives reduce proinflammatory macrophage activation and macrophage\u2010mediated neurotoxicity"],"prefix":"10.1111","volume":"25","author":[{"given":"Bei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Medicine, Spinal Cord and Brain Injury Research Center University of Kentucky Lexington Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Kopper","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Spinal Cord and Brain Injury Research Center University of Kentucky Lexington Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Bioorganic, Medicinal, &amp; 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