Mimicking in vivo Inflammation: A New in vitro Model of Endothelial Inflammation to Advance the Study of IMID-Associated Cardiovascular Diseases
- 1Preclinical Research Department, Labo’life España, Illes Balears, Spain
- 2ProfileHIT, Sainte-Pazanne, France
- 3Preclinical Research Department, Labo’life France, Moncoutant-sur-Sevre, France
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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
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BibTeX
@article{parra2026mimicking,
title = {{Mimicking in vivo Inflammation: A New in vitro Model of Endothelial Inflammation to Advance the Study of IMID-Associated Cardiovascular Diseases}},
author = {Pilar Parra and Benita Mas and Flora Marchand and Mathias Chatelais and Ilaria Floris},
journal = {Journal of Inflammation Research},
year = {2026},
month = oct,
doi = {10.2147/jir.s635143},
url = {https://doi.org/10.2147/jir.s635143},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Mimicking in vivo Inflammation: A New in vitro Model of Endothelial Inflammation to Advance the Study of IMID-Associated Cardiovascular Diseases
AU - Pilar Parra
AU - Benita Mas
AU - Flora Marchand
AU - Mathias Chatelais
AU - Ilaria Floris
PY - 2026
DA - 2026/10/27
JO - Journal of Inflammation Research
DO - 10.2147/jir.s635143
UR - https://doi.org/10.2147/jir.s635143
AB - 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
SN - 1178-7031
ER -