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

Eur J Pharmacol. 2015 Oct 15;765:355-65. doi: 10.1016/j.ejphar.2015.08.054. Epub 2015 Sep 4.


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-α (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-α were evaluated on the leukocyte recruitment induced by a variety of endothelial (TNF-α, interleukin-1β, lymphotoxin-α and angiotensin-II) and leukocyte (PAF, IL-12 and IL-23) stimuli related to inflammation and atherosclerosis. Treatment with anti-TNF-α, even before or after establishing the inflammatory situation induced by TNF-α, 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-α in terms of leukocyte adhesion to endothelium. However, anti-TNF-α drugs did not influence the actions of interleukin-1β, but prevented those of lymphotoxin-α and angiotensin-II. However, once established, inflammatory response elicited by the latter three stimuli could not be reversed. Pre-treatment with anti-TNF-α, 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-α, have the capacity to influence cardiovascular risk accompanying psoriasis and rheumatoid arthritis by ameliorating vascular inflammation.

Keywords: Anti-IL-12/23 agents; Anti-TNF-α agents; Biologics; Cardiovascular side effects; Leukocyte–endothelial cell interactions; Rheumatic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / metabolism*
  • Interleukin-23 / antagonists & inhibitors*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism*


  • Interleukin-23
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Adalimumab