Prasugrel inhibits platelet-enhanced pro-inflammatory CD4+ T cell responses in humans. Issue 1 (March 2015)

• Record Type: Journal Article
• Authors: Johnston, L.R.; La Flamme, A.C.; Larsen, P.D.; Harding, S.A.
• Is Part Of: Atherosclerosis. Volume 239:Issue 1(2015)
• Page Start: 283
• Page End: 286
• Publication Date: 2015-03
• Subjects: Platelets -- Inflammation -- Atherosclerosis -- Antiplatelet therapy; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.01.006
• Languages: English
• ISSNs: 0021-9150

Abstract

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. Highlights: Significant stimulation of CD4 T-cell pro-inflammatory subsets when with platelets compared to T-cells alone. This enhancement was not seen in the anti-inflammatory CD4 T cell subsets. Prasugrel administration resulted in the complete abolishment of this stimulatory effect of platelets on T cells. Prasugrel and other antiplatelet agents may provide immunomodulating benefits in addition to their antithrombotic action.