{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:44:08Z","timestamp":1792691048927,"version":"4.5.0"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish Medical Center, Wesley Medical Center, and McAllen Medical Center, and Intermountain Health affiliated, Lutheran Medical Center"},{"name":"Swedish Medical Center, Wesley Medical Center, and McAllen Medical Center, and Intermountain Health affiliated, Lutheran Medical Center"},{"name":"Swedish Medical Center, Wesley Medical Center, and McAllen Medical Center, and Intermountain Health affiliated, Lutheran Medical Center"},{"name":"Swedish Medical Center, Wesley Medical Center, and McAllen Medical Center, and Intermountain Health affiliated, Lutheran Medical Center"},{"name":"Swedish Medical Center, Wesley Medical Center, and McAllen Medical Center, and Intermountain Health affiliated, Lutheran Medical Center"},{"name":"Swedish Medical Center, Wesley Medical Center, and McAllen Medical Center, and Intermountain Health affiliated, Lutheran Medical Center"},{"name":"Swedish Medical Center, Wesley Medical Center, and McAllen Medical Center, and Intermountain Health affiliated, Lutheran Medical Center"},{"name":"Swedish Medical Center, Wesley Medical Center, and McAllen Medical Center, and Intermountain Health affiliated, Lutheran Medical Center"},{"name":"Swedish Medical Center, Wesley Medical Center, and McAllen Medical Center, and Intermountain Health affiliated, Lutheran Medical Center"},{"name":"Insignia Pharmaceuticals, LLC"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Systemic inflammatory response syndrome, driven by trauma or infection, involves excessive innate immune activation. Dexamethasone (DEX), a synthetic glucocorticoid, suppresses inflammation, although adverse side effects limit its clinical use. The inflammasome, a multiprotein complex that assembles in response to inflammatory stimuli like ATP after lipopolysaccharide (LPS) priming, facilitates caspase-1 cleavage and release of the proinflammatory cytokine, interleukin (IL)-1\u03b2. We investigated whether DEX and decanoic acid (DA), a saturated medium-chain fatty acid, inhibited caspase-1 activity and IL-1\u03b2 release in an LPS\/ATP-stimulated THP-1 macrophage model and whether co-treatment would allow for pharmacologic DEX dose-sparing in vitro. PMA-differentiated THP-1macrophages were primed with LPS overnight and stimulated with ATP for 3 h in the presence of DA, DEX, or both. Viability and cytotoxicity were assessed. Caspase-1 activity and IL-1\u03b2 were quantified, and EC\n                    <jats:sub>50<\/jats:sub>\n                    values were calculated by nonlinear regression. In control conditions, LPS\/ATP stimulation induced 5.56 (q1: 3.51 \u2013 q3: 6.38) ng\/mL of IL-1\u03b2 release. DA and DEX inhibited IL-1\u03b2 with full dose-response EC\n                    <jats:sub>50<\/jats:sub>\n                    values of 131.7 \u03bcM and 24.29 nM, respectively. DA concentrations exceeding 800 \u03bcM decreased cell viability. An 8 x 9-point DA\/DEX dose matrix (0\u2013500 \u03bcM DA; 0 to 1e4 nM DEX) was used to interrogate drug interaction for IL-1\u03b2 inhibition and caspase-1 activity. DEX EC\n                    <jats:sub>50<\/jats:sub>\n                    values remained within a narrow 95% confidence interval of 17.5\u201326.6 nM, regardless of DA background concentration. DA reduced caspase-1 enzymatic activity with a calculated EC\n                    <jats:sub>50<\/jats:sub>\n                    value of ~140 \u03bcM; whereas, DEX did not. These data show that DA and DEX act independently. Furthermore, compared to DEX alone, the presence of DA allowed for equivalent in vitro IL-1\u03b2 suppression at lower DEX concentrations, supporting pharmacologic DEX dose-sparing. Determination of whether this pharmacologic effect translates to clinically meaningful corticosteroid dose reduction requires further study.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0361029","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:32:31Z","timestamp":1792690351000},"page":"e0361029","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decanoic acid additively suppresses IL-1\u03b2 and enables pharmacologic dexamethasone dose-sparing in LPS\/ATP-stimulated THP-1 macrophages"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6916-9774","authenticated-orcid":true,"given":"Melissa A.","family":"Hausburg","sequence":"first","affiliation":[{"name":"Swedish Medical Center","place":["Englewood, Colorado, United States of America"],"department":["Trauma Research"]},{"name":"Wesley Medical 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M.","family":"Madayag","sequence":"additional","affiliation":[{"name":"Lutheran Medical Center","place":["Wheat Ridge, Colorado, United States of America"],"department":["Trauma Services"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos H.","family":"Palacio","sequence":"additional","affiliation":[{"name":"South Texas Health System","place":["McAllen, Texas, United States of America"],"department":["Trauma Services"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8023-2607","authenticated-orcid":true,"given":"Jason S.","family":"Williams","sequence":"additional","affiliation":[{"name":"Swedish Medical Center","place":["Englewood, Colorado, United States of America"],"department":["Trauma Research"]},{"name":"Wesley Medical Center","place":["Wichita, Kansas, United States of America"],"department":["Trauma Research"]},{"name":"Lutheran Medical Center","place":["Wheat Ridge, Colorado, United States of America"],"department":["Trauma Research"]},{"name":"South Texas Health System","place":["McAllen, Texas, United States of America"],"department":["Trauma Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5708-8790","authenticated-orcid":true,"given":"Gregory W.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Swedish Medical Center","place":["Englewood, Colorado, United States of America"],"department":["Trauma Research"]},{"name":"Wesley Medical Center","place":["Wichita, Kansas, United States of America"],"department":["Trauma Research"]},{"name":"Lutheran Medical Center","place":["Wheat Ridge, Colorado, United States of America"],"department":["Trauma Research"]},{"name":"South Texas Health System","place":["McAllen, Texas, United States of America"],"department":["Trauma 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