{
  "abstract": "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)-1β. We investigated whether DEX and decanoic acid (DA), a saturated medium-chain fatty acid, inhibited caspase-1 activity and IL-1β 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-1β were quantified, and EC50 values were calculated by nonlinear regression. In control conditions, LPS/ATP stimulation induced 5.56 (q1: 3.51 – q3: 6.38) ng/mL of IL-1β release. DA and DEX inhibited IL-1β with full dose-response EC50 values of 131.7 μM and 24.29 nM, respectively. DA concentrations exceeding 800 μM decreased cell viability. An 8 x 9-point DA/DEX dose matrix (0–500 μM DA; 0 to 1e4 nM DEX) was used to interrogate drug interaction for IL-1β inhibition and caspase-1 activity. DEX EC50 values remained within a narrow 95% confidence interval of 17.5–26.6 nM, regardless of DA background concentration. DA reduced caspase-1 enzymatic activity with a calculated EC50 value of ~140 μM; 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-1β 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.",
  "abstract_shown": true,
  "affiliations": [
    "Trauma Research, Swedish Medical Center, Englewood, Colorado, United States of America.",
    "Trauma Research, Wesley Medical Center, Wichita, Kansas, United States of America.",
    "Trauma Research, Lutheran Medical Center, Wheat Ridge, Colorado, United States of America.",
    "Trauma Research, South Texas Health System, McAllen, Texas, United States of America.",
    "Trauma Services, Swedish Medical Center, Englewood, Colorado, United States of America.",
    "Emergency Services, Wesley Medical Center, Wichita, Kansas, United States of America.",
    "Trauma Services, Lutheran Medical Center, Wheat Ridge, Colorado, United States of America.",
    "Trauma Services, South Texas Health System, McAllen, Texas, United States of America.",
    "Department of Molecular Biology, Rocky Vista University, Parker, Colorado, United States of America."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
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        0,
        1,
        2,
        3
      ],
      "name": "Melissa A Hausburg",
      "orcid": "0000-0002-6916-9774"
    },
    {
      "affs": [
        4
      ],
      "name": "Kaysie L Banton"
    },
    {
      "affs": [
        5
      ],
      "name": "Christopher D Cassidy"
    },
    {
      "affs": [
        6
      ],
      "name": "Robert M Madayag"
    },
    {
      "affs": [
        7
      ],
      "name": "Carlos H Palacio"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jason S Williams",
      "orcid": "0000-0002-8023-2607"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Gregory W Thomas",
      "orcid": "0000-0002-5708-8790"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Raphael Bar-Or"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        8
      ],
      "name": "David Bar-Or"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e135whnrrcs86.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0361029",
  "fulltext_url": "https://europepmc.org/articles/PMC13690199",
  "id": "e135whnrrcs86",
  "issns": [
    "1932-6203"
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  "landing_url": "https://doi.org/10.1371/journal.pone.0361029",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Inflammasome and immune disorders"
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      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzymes/Proteases"
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      "/Medicine and health sciences/Immunology/Immune system proteins/Inflammasomes"
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  "pdf_url": "https://europepmc.org/articles/PMC13690199?pdf=render",
  "pmcid": "PMC13690199",
  "pmid": "42911967",
  "published": "2026-10-22",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/e135whnrrcs86.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:23Z",
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  "subjects": [
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Decanoic acid additively suppresses IL-1β and enables pharmacologic dexamethasone dose-sparing in LPS/ATP-stimulated THP-1 macrophages",
  "title_text": "Decanoic acid additively suppresses IL-1β and enables pharmacologic dexamethasone dose-sparing in LPS/ATP-stimulated THP-1 macrophages",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/e135whnrrcs86",
  "venue": "PLOS One",
  "versions": []
}