Interleukin-1β exacerbates disease and is a potential therapeutic target to reduce pulmonary inflammation during severe influenza A virus infection,Immunology and Cell Biology

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Interleukin-1β exacerbates disease and is a potential therapeutic target to reduce pulmonary inflammation during severe influenza A virus infection
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2021-04-09 , DOI: 10.1111/imcb.12459
Abdullah Bawazeer _{1,

2} , Sarah Rosli _{1,

2} , Christopher M Harpur _{1,

2} , Callum AH Docherty _{1,

2} , Ashley Mansell _{1,

2} , Michelle D Tate _{1,

2}

Affiliation

Hyperinflammatory responses including the production of NLRP3-dependent interleukin (IL)-1β is a characteristic feature of severe and fatal influenza A virus (IAV) infections. The NLRP3 inflammasome has been shown to play a temporal role during severe IAV immune responses, with early protective and later detrimental responses. However, the specific contribution of IL-1β in modulating IAV disease in vivo is currently not well defined. Here, we identified that activation of NLRP3-dependent IL-1β responses occurs rapidly following HKx31 H3N2 infection, prior to the onset of severe IAV disease. Mature IL-1β was detectable in vivo in both hemopoietic and nonhemopoietic cells. Significantly, therapeutic inhibition of IL-1β in the airways with intranasal anti-IL-1β antibody treatment from day 3 postinfection, corresponding to the onset of clinical signs of disease, significantly prolonged survival and reduced inflammation in the airways. Importantly, early targeting of IL-1β from day 1 postinfection also improved survival. Together, these studies specifically define a role for IL-1β in contributing to the development of hyperinflammation and disease and indicate that targeting IL-1β is a potential therapeutic strategy for severe IAV infections.

中文翻译：

白细胞介素-1β 会加剧疾病，是减轻严重甲型流感病毒感染期间肺部炎症的潜在治疗靶点

包括产生 NLRP3 依赖性白细胞介素 (IL)-1β 在内的高炎症反应是严重和致命的甲型流感病毒 (IAV) 感染的特征。NLRP3 炎症小体已被证明在严重的 IAV 免疫反应中发挥时间作用，具有早期保护性反应和后期有害反应。然而，IL-1β在体内调节 IAV 疾病的具体作用目前尚未明确。在这里，我们发现 NLRP3 依赖性 IL-1β 反应的激活在 HKx31 H3N2 感染后迅速发生，在严重 IAV 疾病发作之前。在体内可检测到成熟的 IL-1β在造血细胞和非造血细胞中。值得注意的是，从感染后第 3 天起，鼻内抗 IL-1β 抗体治疗对气道中 IL-1β 的治疗性抑制，对应于疾病的临床症状的出现，显着延长了存活并减少了气道中的炎症。重要的是，从感染后第 1 天开始早期靶向 IL-1β 也提高了存活率。总之，这些研究明确定义了 IL-1β 在促进过度炎症和疾病发展中的作用，并表明靶向 IL-1β 是严重 IAV 感染的潜在治疗策略。

更新日期：2021-04-09

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