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Early IL-2 treatment of mice with Pseudomonas aeruginosa pneumonia induced PMN-dominating response and reduced lung pathology.
APMIS ( IF 2.2 ) Pub Date : 2020-08-13 , DOI: 10.1111/apm.13072
Henrik Pierre Calum 1, 2 , Claus Moser 2 , Peter Ostrup Jensen 2, 3 , Thomas Bjarnsholt 2, 3 , Michael Givskov 3 , Niels Høiby 2, 3
Affiliation  

IL‐2 is a pro‐inflammatory and a Th1 inducing cytokine, which is important for activation of the cell‐mediated immunity. IL‐2 in serum and sputum has been observed to be reduced in cystic fibrosis (CF) patients. The present IL‐2 treatment study of Pseudomonas aeruginosa (PA) lung infected mice was performed in order to evaluate the effect of IL‐2 supplement. One hundred‐and‐twenty female BALB/c mice were divided into three groups: 1) IL‐2 treatment/infection (TIG), 2) non‐treatment/infection (NTIG), and 3) IL‐2 treatment/non‐infection (TNIG). The mice were challenged intra‐tracheally with PA (PAO579) embedded in seaweed alginate to resemble the biofilm mode of growth. At day 0 and 1, the treatment groups received IL‐2 s.c. Mice were killed on day 1 or 2, and cytokine production, lung pathology, and quantitative lung bacteriology were estimated. IL‐2 treatment of infected mice reduced the number of mice with signs of macroscopic lung pathology at day 2 (p < 0.05). The reduced macroscopic pathology was paralleled by a reduced IL‐1β and TNF‐α. In contrast, an increased PMN response at day 2 was observed in the IL‐2 treated mice (p < 0.01). This was preceded by a significantly higher degree of microscopic inflammation at day 1 (p < 0.02). The IL‐12 levels decreased in both groups of infected mice at day 2 (p < 0.01), however, significantly more in the IL‐2 treated mice (p < 0.02). In accordance, but surprisingly, IFN‐γ was significantly reduced in the IL‐2 treated PA infected group at day 2 (p < 0.05). The present results indicate that early IL‐2 treatment prolongs the PMN response but also reduces pro‐inflammatory IL‐1β and TNF‐α and macroscopic signs of pathology.

中文翻译:

铜绿假单胞菌肺炎小鼠的早期IL-2治疗诱导了PMN主导反应并降低了肺部病理。

IL-2是促炎和Th1诱导的细胞因子,对激活细胞介导的免疫至关重要。在囊性纤维化(CF)患者中,血清和痰中的IL-2含量降低。当前铜绿假单胞菌的IL-2治疗研究(PA)进行了肺部感染的小鼠,以评估补充IL-2的效果。120只雌性BALB / c小鼠分为三组:1)IL-2治疗/感染(TIG),2)非治疗/感染(NTIG)和3)IL-2治疗/非感染感染(TNIG)。气管内用海藻藻酸盐中嵌入的PA(PAO579)攻击小鼠,类似于生物膜的生长方式。在第0天和第1天,接受IL-2 sc小鼠的治疗组在第1天或第2天被杀死,并评估细胞因子的产生,肺病理学和定量肺细菌学。IL-2治疗感染的小鼠在第2天减少了出现宏观肺部病理征象的小鼠数量(p <0.05)。减少的宏观病理学与减少的IL-1β和TNF-α相平行。相反,在经IL-2治疗的小鼠中,在第2天观察到PMN反应增强(p <0.01)。在此之前的第1天,显微镜下炎症的程度明显更高(p <0.02)。在第2天,两组受感染小鼠的IL-12水平均下降(p <0.01),但经IL-2处理的小鼠中IL-12水平明显更高(p <0.02)。同样,但令人惊讶的是,在第2天经IL-2治疗的PA感染组中IFN-γ显着降低(p <0.05)。目前的结果表明,早期的IL-2治疗可延长PMN反应,但也可降低促炎性IL-1β和TNF-α以及病理的宏观征象。但是,经IL-2治疗的小鼠中的含量明显更高(p <0.02)。同样,但令人惊讶的是,在第2天经IL-2治疗的PA感染组中IFN-γ明显降低(p <0.05)。目前的结果表明,早期的IL-2治疗可延长PMN反应,但也可降低促炎性IL-1β和TNF-α以及病理的宏观征象。但是,经IL-2治疗的小鼠中的含量明显更高(p <0.02)。同样,但令人惊讶的是,在第2天经IL-2治疗的PA感染组中IFN-γ显着降低(p <0.05)。目前的结果表明,早期的IL-2治疗可延长PMN反应,但也可降低促炎性IL-1β和TNF-α以及病理的宏观征象。
更新日期:2020-08-13
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