Prasugrel inhibits platelet-enhanced pro-inflammatory CD4+ T cell responses in humans

Atherosclerosis. 2015 Mar;239(1):283-6. doi: 10.1016/j.atherosclerosis.2015.01.006. Epub 2015 Jan 14.

Abstract

While platelets have well characterized effects on monocytes, the effect of platelet activation on CD4+ T-cell differentiation and cytokine production is not clear. To examine the effects of platelet T-cell interactions on T-cell phenotype, and whether these interactions were altered by prasugrel, we conducted a randomized, double-blind, placebo-controlled crossover study in healthy subjects. At baseline the addition of platelets to CD4+ T-cells resulted in an increase in the release of pro-inflammatory cytokine IFN-γ (192% increase in IFN-γ levels, p = 0.01) and pro-inflammatory CD4+ phenotypes, (38% and 58% increase in Th1 and Th17 phenotypic markers respectively, p = 0.01) but no change in Tregs. Prasugrel abolished the effects of platelets on CD4+ T-cells with similar levels of pro-inflammatory cytokines and cell numbers to T-cells stimulated. Antiplatelet therapy may provide therapeutic benefit both from direct platelet inhibition and also through indirect effects on immune response development.

Keywords: Antiplatelet therapy; Atherosclerosis; Inflammation; Platelets.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Platelets / drug effects*
  • CD4-Positive T-Lymphocytes / cytology*
  • Cell Differentiation
  • Cross-Over Studies
  • Cytokines / metabolism
  • Fibrinolytic Agents / therapeutic use
  • Flow Cytometry
  • Humans
  • Inflammation / drug therapy*
  • Middle Aged
  • Platelet Activation
  • Prasugrel Hydrochloride / therapeutic use*
  • Prospective Studies
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Young Adult

Substances

  • Cytokines
  • Fibrinolytic Agents
  • Prasugrel Hydrochloride