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低剂量乙酰水杨酸可降低 T 细胞免疫激活:对 HIV 预防的潜在影响。

Low-Dose Acetylsalicylic Acid Reduces T Cell Immune Activation: Potential Implications for HIV Prevention.

机构信息

Laboratory of Viral Immunology, Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.

Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.

出版信息

Front Immunol. 2021 Nov 18;12:778455. doi: 10.3389/fimmu.2021.778455. eCollection 2021.

Abstract

INTRODUCTION

Acetylsalicylic acid (ASA) is a well-known and safe anti-inflammatory. At low-dose, it is prescribed to prevent secondary cardiovascular events in those with pre-existing conditions and to prevent preeclampsia. Little is known about how low-dose ASA affects the immune response. In this study, we followed women to assess how ASA use modifies T cells immune phenotypes in the blood and at the genital tract.

METHODS

HIV uninfected women from Kenya were enrolled in this study and followed for one month to assess baseline responses including systemic/mucosal baseline immune activation. Participants then received 81mg of ASA daily for 6 weeks to assess changes to T cell immune activation (systemic and mucosal) relative to baseline levels.

RESULTS

The concentration of ASA measured in the blood was 58% higher than the level measured at the female genital tract. In the blood, the level of ASA was inversely correlated with the following: the proportion of Th17 expressing HLA-DR (p=0.04), the proportion of effector CD4 T cells expressing CCR5 (p=0.03) and the proportion of CD8Tc17 expressing CCR5 (p=0.04). At the genital tract, ASA use correlated with a decreased of activated CD4T cells [CD4CCR5CD161 (p=0.02) and CD4CCR5CD95 (p=0.001)].

CONCLUSION

This study shows that ASA use impacts the immune response in both the systemic and genital tract compartments. This could have major implications for the prevention of infectious diseases such as HIV, in which the virus targets activated T cells to establish an infection. This could inform guidelines on ASA use in women.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov, identifier NCT02079077.

摘要

简介

乙酰水杨酸(ASA)是一种众所周知的安全的抗炎药。低剂量时,它被用于预防已有疾病的人发生二次心血管事件和预防子痫前期。对于低剂量 ASA 如何影响免疫反应,人们知之甚少。在这项研究中,我们对女性进行了随访,以评估 ASA 的使用如何改变血液和生殖道中的 T 细胞免疫表型。

方法

本研究纳入了肯尼亚的 HIV 阴性女性,并对其进行了一个月的随访,以评估包括全身/黏膜基线免疫激活在内的基线反应。然后,参与者每天服用 81mg 的 ASA,持续 6 周,以评估相对于基线水平的 T 细胞免疫激活(全身和黏膜)的变化。

结果

血液中 ASA 的浓度比生殖道中测量的浓度高 58%。在血液中,ASA 的水平与以下因素呈负相关:表达 HLA-DR 的 Th17 比例(p=0.04)、表达 CCR5 的效应性 CD4 T 细胞比例(p=0.03)和表达 CCR5 的 CD8Tc17 比例(p=0.04)。在生殖道中,ASA 的使用与激活的 CD4T 细胞的减少相关[CD4CCR5CD161(p=0.02)和 CD4CCR5CD95(p=0.001)]。

结论

这项研究表明,ASA 的使用会影响全身和生殖道两个部位的免疫反应。这可能对预防 HIV 等传染病有重大影响,因为病毒会靶向激活的 T 细胞以建立感染。这可以为女性使用 ASA 的指南提供信息。

临床试验注册

ClinicalTrials.gov,标识符 NCT02079077。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9619/8637415/04b966959bd8/fimmu-12-778455-g001.jpg

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