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秋水仙碱可降低 COVID-19 患者中 NLRP3 炎症小体的激活。

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

机构信息

Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, 14.048-900, São Paulo, Brazil.

Department of Cell Biology, University of São Paulo, Ribeirao Preto, São Paulo, Brazil.

出版信息

Inflamm Res. 2023 May;72(5):895-899. doi: 10.1007/s00011-023-01718-y. Epub 2023 Mar 14.

Abstract

OBJECTIVE

To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19.

METHODS

We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1β, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days.

RESULTS

Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1β.

CONCLUSION

Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19.

TRIAL REGISTRATION NUMBERS

RBR-8jyhxh.

摘要

目的

评估秋水仙碱治疗是否与抑制 COVID-19 患者 NLRP3 炎性体激活有关。

方法

我们对秋水仙碱治疗 COVID-19 的双盲安慰剂对照随机临床试验(RCT)进行了事后分析。在接受标准治疗(SOC)加安慰剂与接受 SOC 加秋水仙碱的患者中,在入组时和治疗后 48-72 小时评估 NOD 样受体蛋白 3(NLRP3)炎性体产物-活性半胱天冬酶-1(Casp1p20)、IL-1β和 IL-18 的血清水平。秋水仙碱方案为每天 tid 0.5mg,连用 5 天,然后每天 bid 0.5mg,再连用 5 天。

结果

36 例患者接受 SOC 加秋水仙碱治疗,36 例患者接受 SOC 加安慰剂治疗。秋水仙碱降低了补充氧气的需求和住院时间。在第 2-3 天,秋水仙碱降低了 Casp1p20 和 IL-18 的血清水平,但没有降低 IL-1β。

结论

秋水仙碱治疗抑制了 NLRP3 炎性体的激活,这是 COVID-19 中“细胞因子风暴”的触发因素。

试验注册号

RBR-8jyhxh。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5226/10013297/c4601dcee39b/11_2023_1718_Fig1_HTML.jpg

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