{
  "abstract": "Background: Patients with immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and systemic lupus erythematosus (SLE), face a markedly increased risk of cardiovascular disease (CVD). This is mainly driven by chronic systemic inflammation, which in turn triggers endothelial activation and dysfunction.\n\nObjective: We aimed to establish a pathophysiologically relevant in vitro endothelial activation model using sub-nanogram concentrations of cytokines to mimic the low-grade systemic inflammatory milieu observed in active IMIDs.\n\nMethods: Human umbilical vein endothelial cells (HUVECs) were exposed to a combination of three key proinflammatory cytokines at circulating pathophysiological concentrations, representative of active clinical disease —interleukin-1 beta (IL-1β) at 20 pg/mL, tumor necrosis factor (TNF-α) at 50 pg/mL, and interferon-gamma (IFN-γ) at 100 pg/mL— referred to as the MIX. Each individual cytokine was also tested, and a high-dose IL-1β control (10 ng/mL) was included as a standard supra-physiological positive control. Surface marker expression was analyzed by flow cytometry, and cytokine/chemokine release was quantified by multiplex assay.\n\nResults: At 24 h, the MIX triggered a particular endothelial activation state. Notably, it significantly upregulated key immunological surface markers, including vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1), compared to the untreated control. Furthermore, the MIX significantly increased the release of key chemokines, such as IL-8, interferon-gamma inducible protein-10 (IP-10), and monocyte chemotactic protein-1 (MCP-1), displaying a distinct cooperative profile compared to individual low-dose cytokines.\n\nConclusion: Our study demonstrates that the combination of IL-1β, TNF-α, and IFN-γ at pathophysiologically relevant, sub-nanogram concentrations, can successfully model key features of IMID-associated endothelial activation by driving immune marker upregulation and secretory activity, opening new avenues towards the development of physiologically relevant in vitro system for future research into IMID-associated CVD.",
  "abstract_shown": true,
  "affiliations": [
    "Preclinical Research Department, Labo’life España, Illes Balears, Spain",
    "ProfileHIT, Sainte-Pazanne, France",
    "Preclinical Research Department, Labo’life France, Moncoutant-sur-Sevre, France"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Pilar Parra",
      "orcid": "0009-0005-6492-9171"
    },
    {
      "affs": [
        0
      ],
      "name": "Benita Mas",
      "orcid": "0009-0000-4271-7331"
    },
    {
      "affs": [
        1
      ],
      "name": "Flora Marchand"
    },
    {
      "affs": [
        1
      ],
      "name": "Mathias Chatelais"
    },
    {
      "affs": [
        2
      ],
      "name": "Ilaria Floris",
      "orcid": "0000-0003-4089-3133"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c2vjckkrkb4f9.bib",
  "cited_by": 0,
  "doi": "10.2147/jir.s635143",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723236/",
  "id": "c2vjckkrkb4f9",
  "issns": [
    "1178-7031"
  ],
  "landing_url": "https://doi.org/10.2147/jir.s635143",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2403|Atherosclerosis and Cardiovascular Diseases"
    ]
  ],
  "openalex": "W7223811243",
  "pdf_url": "https://www.dovepress.com/article/download/121423",
  "pmcid": "PMC13723236",
  "pmid": "42967185",
  "published": "2026-10-27",
  "publisher": "Dove Press",
  "ris": "https://research.draconitic.com/paper/c2vjckkrkb4f9.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:21:52Z",
      "native_id": "PMC13723236",
      "source": "pmc",
      "url": "https://doi.org/10.2147/jir.s635143"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Atherosclerosis and Cardiovascular Diseases",
      "subfield": "immunology"
    }
  ],
  "title": "Mimicking in vivo Inflammation: A New in vitro Model of Endothelial Inflammation to Advance the Study of IMID-Associated Cardiovascular Diseases",
  "title_text": "Mimicking in vivo Inflammation: A New in vitro Model of Endothelial Inflammation to Advance the Study of IMID-Associated Cardiovascular Diseases",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:52Z",
  "url": "https://research.draconitic.com/paper/c2vjckkrkb4f9",
  "venue": "Journal of Inflammation Research",
  "versions": []
}