Differential effects of anti-TNF-a and anti-IL-12/23 agents on human leukocyte-endothelial cell interactions.


Por: Ríos-Navarro C, de Pablo C, Collado-Diaz V, Orden S, Blas-Garcia A, Martínez-Cuesta MÁ, Esplugues JV and Alvarez A

Fecha de Publicación: 15/10/2015
Categoría: Pharmacology

Resumen:
Enhanced leukocyte recruitment is an inflammatory process that occurs during early phases of the vascular dysfunction that characterises atherosclerosis. We evaluated the impact of anti-TNF-a (adalimumab, infliximab and etanercept) and anti-IL-12/23 (ustekinumab) on interactions between human leukocytes and endothelial cells in a flow chamber that reproduced in vivo conditions. Clinical concentrations of anti-TNF-a were evaluated on the leukocyte recruitment induced by a variety of endothelial (TNF-a, interleukin-1ß, lymphotoxin-a and angiotensin-II) and leukocyte (PAF, IL-12 and IL-23) stimuli related to inflammation and atherosclerosis. Treatment with anti-TNF-a, even before or after establishing the inflammatory situation induced by TNF-a, diminished leukocyte-endothelial cell interactions induced by this stimuli. Our results also implicated adhesion molecules (ICAM-1, VCAM-1 and E-selectin) in the actions of anti-TNF-a in terms of leukocyte adhesion to endothelium. However, anti-TNF-a drugs did not influence the actions of interleukin-1ß, but prevented those of lymphotoxin-a and angiotensin-II. However, once established, inflammatory response elicited by the latter three stimuli could not be reversed. Pre-treatment with anti-TNF-a, also prevented leukocyte actions induced by IL-23 on PBMC rolling flux and rolling velocity and by IL-12 on PMN adhesion. Ustekinumab exhibited a more discreet profile, having no effect on leukocyte recruitment induced by any of the endothelial stimuli, while blocking the effects of IL-23 on leukocyte activation and those of IL-12 on PMN adhesion and PAF on PBMC rolling velocity. These findings endorse the idea that biological anti-inflammatory drugs, in particular anti-TNF-a, have the capacity to influence cardiovascular risk accompanying psoriasis and rheumatoid arthritis by ameliorating vascular inflammation.

Direcciones
Ríos-Navarro C: Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain; FISABIO- Hospital Universitario Dr. Peset, Valencia, Spain
de Pablo C: Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain
Collado-Diaz V: Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain; FISABIO- Hospital Universitario Dr. Peset, Valencia, Spain
Orden S: Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain; FISABIO- Hospital Universitario Dr. Peset, Valencia, Spain
Blas-Garcia A: Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain; FISABIO- Hospital Universitario Dr. Peset, Valencia, Spain
Martínez-Cuesta MÁ: Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain
Esplugues JV: Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain; FISABIO- Hospital Universitario Dr. Peset, Valencia, Spain
Alvarez A: Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain; Fundación General Universidad de Valencia, Valencia, Spain
ISSN: 00142999





EUR J PHARMACOL
Editorial
ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS, Países Bajos
Tipo de documento: Article
Volumen: 765 Número:
Páginas: 355-365s
WOS: 000364249100044
ID de PubMed: 26344475

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