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Early IL‐2 treatment of mice with Pseudomonas aeruginosa pneumonia induced PMN‐dominating response and reduced lung pathology
Author(s) -
Calum Henrik Pierre,
Moser Claus,
Jensen Peter Ostrup,
Bjarnsholt Thomas,
Givskov Michael,
Høiby Niels
Publication year - 2020
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.13072
Subject(s) - lung , cytokine , pneumonia , pseudomonas aeruginosa , sputum , inflammation , medicine , interleukin 10 , immunology , cystic fibrosis , interleukin , pathology , biology , tuberculosis , bacteria , genetics
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.