Figure 3.
Figure 3. TXA changes plasma cytokine levels and functional marker expression on myeloid cell populations in healthy volunteers. Plasma cytokine levels and expression of functional markers on myeloid cells were evaluated in healthy volunteers at various time points after administration of TXA. TXA significantly reduced plasma levels of the proinflammatory cytokine TNF-α at 4 hours, as well as IL-6 between 2 hours and 24 hours. (Ai) Levels of the type 1 T helper cell cytokine IFN-γ were significantly reduced at 2 hours and 4 hours, and the levels of the type 2 T helper cell cytokine IL-10 were significantly reduced at 2 hours (n = 9). (Aii) sTNFR2 levels were significantly enhanced by TXA at 2 hours and 4 hours but returned to baseline at 24 hours (n = 9). (B) Levels of circulating nonclassical monocytes were significantly enhanced by TXA after 24 hours, whereas pDC levels were reduced after 4 hours, yet returned to baseline levels after 24 hours (n = 6). (C) TXA significantly increased expression of the activation marker CD83 on classical and intermediate monocytes, as well as on CD1c+ cDCs (n = 6). (D) The maturation marker HLA-DR was reduced at 24 hours on intermediate monocytes (already at 4 hours), classical monocytes, and pDCs (n = 6). (E) CCR7, indicating migration to secondary lymphatic organs, was significantly reduced by TXA in classical and intermediate monocytes (n = 6). (F) TNFR2, mediating TNF-α signaling, was increased at 4 hours and 24 hours in classical and intermediate monocytes and CD1c+ cDCs, as well as in pDCs at 24 hours after TXA intake (n = 6). (G) PD-L1, which induces programmed cell death in effector cells of the immune system, was significantly downregulated by TXA after 4 hours and even further after 24 hours in classical monocytes and intermediate monocytes, as well as in CD1c+ cDCs and the immunosuppressive monocytic myeloid-derived suppressor cell (MO-MDSC) at 24 hours (n = 6). Data are expressed as mean ± standard error of the mean. *P < .05, **P < .01, ***P < .001, repeated measures 1-way ANOVA with Dunnett’s correction test for multiple comparisons.

TXA changes plasma cytokine levels and functional marker expression on myeloid cell populations in healthy volunteers. Plasma cytokine levels and expression of functional markers on myeloid cells were evaluated in healthy volunteers at various time points after administration of TXA. TXA significantly reduced plasma levels of the proinflammatory cytokine TNF-α at 4 hours, as well as IL-6 between 2 hours and 24 hours. (Ai) Levels of the type 1 T helper cell cytokine IFN-γ were significantly reduced at 2 hours and 4 hours, and the levels of the type 2 T helper cell cytokine IL-10 were significantly reduced at 2 hours (n = 9). (Aii) sTNFR2 levels were significantly enhanced by TXA at 2 hours and 4 hours but returned to baseline at 24 hours (n = 9). (B) Levels of circulating nonclassical monocytes were significantly enhanced by TXA after 24 hours, whereas pDC levels were reduced after 4 hours, yet returned to baseline levels after 24 hours (n = 6). (C) TXA significantly increased expression of the activation marker CD83 on classical and intermediate monocytes, as well as on CD1c+ cDCs (n = 6). (D) The maturation marker HLA-DR was reduced at 24 hours on intermediate monocytes (already at 4 hours), classical monocytes, and pDCs (n = 6). (E) CCR7, indicating migration to secondary lymphatic organs, was significantly reduced by TXA in classical and intermediate monocytes (n = 6). (F) TNFR2, mediating TNF-α signaling, was increased at 4 hours and 24 hours in classical and intermediate monocytes and CD1c+ cDCs, as well as in pDCs at 24 hours after TXA intake (n = 6). (G) PD-L1, which induces programmed cell death in effector cells of the immune system, was significantly downregulated by TXA after 4 hours and even further after 24 hours in classical monocytes and intermediate monocytes, as well as in CD1c+ cDCs and the immunosuppressive monocytic myeloid-derived suppressor cell (MO-MDSC) at 24 hours (n = 6). Data are expressed as mean ± standard error of the mean. *P < .05, **P < .01, ***P < .001, repeated measures 1-way ANOVA with Dunnett’s correction test for multiple comparisons.

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