IL-1 receptor antagonist reduces endotoxin-induced airway inflammation in healthy volunteers.
IL-1 receptor antagonist reduces endotoxin-induced airway inflammation in healthy volunteers.
复制标题
DOI：
10.1016/j.jaci.2014.07.039
复制
发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Peden DB
中科院分区：
文献类型：
--
作者：
Hernandez ML;Mills K;Almond M;Todoric K;Aleman MM;Zhang H;Zhou H;Peden DB
Asthma with neutrophil predominance is challenging to treat with corticosteroids. Novel treatment options for asthma include those that target innate immune activity. Recent literature has indicated a significant role for IL-1β in both acute and chronic neutrophilic asthma. This study used inhaled endotoxin (LPS) challenge as a model of innate immune activation to a) assess the safety of the interleukin-1 receptor antagonist, anakinra, in conjunction with inhaled LPS and b) to test the hypothesis that IL-1 blockade will suppress acute neutrophil response to challenge with inhaled LPS. In a phase I clinical study, 17 healthy volunteers completed a double-blinded, placebo controlled crossover study where they received 2 daily subcutaneous doses of 1 mg/kg anakinra (maximum dose of 100 mg) or saline (placebo). One hour after the second treatment dose, subjects underwent an inhaled LPS challenge. Induced sputum was assessed for neutrophils 4 hours after inhaled LPS. The effect of anakinra compared to placebo on airway neutrophils and airway pro-inflammatory cytokines after LPS challenge was compared using a linear mixed model approach. Anakinra pretreatment significantly diminished airway neutrophilia compared to placebo. LPS-induced IL-1β, IL-6, and IL-8 were significantly reduced during the anakinra treatment period compared to placebo. Subjects tolerated the anakinra treatment well, without increased frequency of infections that were attributable to anakinra treatment. Anakinra effectively reduced airway neutrophilic inflammation and resulted in no serious adverse events in a model of inhaled LPS challenge. Anakinra is a potential therapeutic candidate for treatment of asthma with neutrophil predominance in diseased populations.
登录
查看更多内容
影响因子：
2.1
作者：
Hernandez ML;Harris B;Lay JC;Bromberg PA;Diaz-Sanchez D;Devlin RB;Kleeberger SR;Alexis NE;Peden DB
通讯作者：
Peden DB
影响因子：
2.8
作者：
Konno, S;Gonokami, Y;Adachi, M
通讯作者：
Adachi, M
影响因子：
14.2
作者：
Alexis, NE;Lay, JC;Becker, S
通讯作者：
Becker, S
影响因子：
14.2
作者：
Alexis, Neil E.;Zhou, Haibo;Peden, David B.
通讯作者：
Peden, David B.
影响因子：
15.9
作者：
Lilly, CM;Nakamura, H;Luster, AD
通讯作者：
Luster, AD