Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage

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Intracerebral hemorrhage(ICH) leads to high rates of death and disability. The pronounced infl ammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma,but the mechanisms remain unknown. In this study,we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage(ICH). The results showed that fingolimod decreased the numbers of circulating CD4~+ T,CD8~+ T,CD(19)~+B,NK,and NKT cells and they recovered quickly after the drug was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly,fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced r T1%. In conclusion,modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability. The pronounced infl ammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrates that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage (ICH). The results showed that fingolimod decreased the numbers of circulating CD4 ~ + T, CD8 ~ + T, CD (19) ~ + B, NK, and NKT cells and they has been quickly after the drug was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced r T1%. In conclusion, modulation of systemic inflammation by fingolimod demonstr ates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.
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