Anti-platelet drugs attenuate the expansion of circulating CD14highCD16+ monocytes under pro-inflammatory conditions.

Aims: Levels of circulating CD14(high)CD16(+) monocytes increase in atherosclerotic patients and are predictive of future cardiovascular events. Platelet activation has been identified as a crucial determinant in the acquisition of a CD16(+) phenotype by classical CD14(high)CD16(-) cells. We tested the hypothesis that anti-platelet drugs modulate the phenotype of circulating monocytes.

Methods And Results: Sixty healthy subjects undergoing influenza immunization were randomly assigned to either no treatment or anti-platelet therapy, namely aspirin 300 mg or 75 mg daily, or clopidogrel (300 mg loading dose followed by 75 mg), for 48 h post-immunization (n = 15/group). Monocyte subsets, high-sensitivity C-reactive protein, pro-inflammatory cytokines, and P-selectin were measured at baseline and post-immunization. The CD14(high)CD16(+) monocyte cell count rose by 67.3% [interquartile range (IQR): 35.7/169.2; P = 0.0002 vs. baseline] in untreated participants. All anti-platelet regimes counteracted expansion of this monocytic subpopulation. Although no statistical differences were noted among the three treatments, aspirin 300 mg was the most efficacious compared with the untreated group (-12.5% change from baseline; IQR: -28.7/18.31; P = 0.001 vs. untreated). Similarly, the rise in P-selectin (17%; IQR: -5.0/39.7; P = 0.03 vs. baseline) observed in untreated participants was abolished by all treatments, with aspirin 300 mg exerting the strongest effect (-30.7%; IQR: -58.4/-0.03; P = 0.007 vs. untreated). Changes in P-selectin levels directly correlated with changes in CD14(high)CD16(+) cell count (r = 0.5; P = 0.0002). There was a similar increase among groups in high-sensitivity C-reactive protein (P < 0.03 vs. baseline levels).

Conclusions: Anti-platelet drugs exert an immunomodulatory action by counteracting CD14(high)CD16(+) monocyte increase under pro-inflammatory conditions, with this effect being dependent on the amplitude of P-selectin reduction.