title: Prasugrel inhibits platelet-enhanced pro-inflammatory CD4+ T cell responses in humans.
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.
authors: Victoria University of Wellington, Wellington, New Zealand; Wellington Cardiovascular Research Group, Wellington, New Zealand. Electronic address: lisa.johnston@vuw.ac.nz.
authors: L R
authors: LR
authors: Johnston
authors: Victoria University of Wellington, Wellington, New Zealand; Wellington Cardiovascular Research Group, Wellington, New Zealand; Malaghan Institute of Medical Research, Wellington, New Zealand.
authors: A C
authors: AC
authors: La Flamme
authors: Victoria University of Wellington, Wellington, New Zealand; Wellington Cardiovascular Research Group, Wellington, New Zealand; University of Otago, Wellington, New Zealand.
authors: P D
authors: PD
authors: Larsen
authors: Victoria University of Wellington, Wellington, New Zealand; Wellington Cardiovascular Research Group, Wellington, New Zealand; Department of Cardiology, Wellington Hospital, Wellington, New Zealand.
authors: S A
authors: SA
authors: Harding
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008875:Middle Aged; D015539:Platelet Activation; D000068799:Prasugrel Hydrochloride / Q000627:therapeutic use*; D011446:Prospective Studies; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: D016207:Cytokines; D005343:Fibrinolytic Agents; D000068799:Prasugrel Hydrochloride
keywords: Antiplatelet therapy; Atherosclerosis; Inflammation; Platelets