{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:26:55Z","timestamp":1791498415046,"version":"4.3.4"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation","award":["GENIUS-2"],"award-info":[{"award-number":["GENIUS-2"]}]},{"name":"Michael Smith Foundation for Health Research Postdoctoral Fellowship","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT 168838"],"award-info":[{"award-number":["PJT 168838"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100023558","name":"Providence Health Care Research Institute","doi-asserted-by":"crossref","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100023558","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"crossref","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,22]]},"abstract":"<jats:p>\n                    Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in\n                    <jats:italic>APOE*3-Leiden.CETP<\/jats:italic>\n                    mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    \u2013induced sepsis in\n                    <jats:italic>APOE*3-Leiden.CETP<\/jats:italic>\n                    and\n                    <jats:italic>APOA1.CETP<\/jats:italic>\n                    mice. Mechanistically, CETP inhibition reduced the host proinflammatory response via attenuation of proinflammatory cytokine transcription and release. This effect was dependent on the presence of HDL, leading to attenuation of immune-mediated organ damage. In addition, CETP inhibition promoted monocyte activation in the blood prior to the onset of sepsis, resulting in accelerated macrophage recruitment to the lung and liver. In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.173205","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T10:22:17Z","timestamp":1713867737000},"source":"Crossref","is-referenced-by-count":17,"title":["CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia\u2013associated mortality in mice"],"prefix":"10.1172","volume":"9","author":[{"given":"Haoyu","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Medicine, Faculty of Medicine,"},{"name":"Centre for Heart and Lung Innovation, St. Paul\u2019s Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3401-4262","authenticated-orcid":true,"given":"Wan Yi","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and 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