[The effect of recombinant interleukin-10/Fc fusion protein on lipopolysaccharide-induced acute lung injury in mice].
OBJECTIVE
To clarify the regulatory role and mechanism of recombinant interleukin-10/Fc (rIL-10/Fc) fusion protein on inflammatory parameters during development of acute lung injury (ALI) induced by lipopolysaccharide (LPS) in a murine model.


METHODS
An ALI model was reproduced by intra-tracheal injection of LPS. rIL-10/Fc was administered intraperitoneally. One hundred and thirty-two BALB/c mice were divided into four groups, including saline control group, rIL-10/Fc control group, ALI model group, and rIL-10/Fc treatment group. Twenty-four-hour survival rate was determined in 25 mice of each group. The number of inflammatory cells and inflammatory mediators in bronchial-alveolar lavage fluid (BALF), tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta, and also lung myeloperoxidase (MPO) activity, lung wet/dry (W/D) ratio were determined in the rest of mice. Pathological changes in lung were examined with hematoxylin-eosin (HE) staining, and inflammatory change was evaluated under microscope.


RESULTS
Levels of TNF-alpha and IL-1 beta in BALF were substantially increased 4 hours after intra-tracheal LPS (both P<0.01), and they were lowered but without significant difference after rIL-10/Fc administration. However, rIL-10/Fc fusion protein markedly attenuated release of TNF-alpha at 8 hours and 12 hours, and IL-1 beta was lowered at 12 hours after LPS challenge. Pre-treatment with rIL-10/Fc fusion protein significantly improved survival rate at 24 hours in LPS challenged mice (P<0.01). There was no significant difference in cell count in BALF, MPO, lung W/D ratio, after treatment of rIL-10/Fc fusion protein. Obvious inflammatory changes were found in lung was found pathologically at 24 hours after LPS injection, but there was no significant difference compared with ALI mice with rIL-10/Fc fusion protein administration.


CONCLUSIONS
rIL-10/Fc fusion protein inhibits release of TNF-alpha and IL-1 beta in BALF in a LPS-induced ALI murine model. rIL-10/Fc fusion protein improves survival rate in ALI mice by decreasing the release of pro-inflammatory cytokines.
Bi
Ming-hua
MH
Medical and Health Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. bmh_119@hotmail.com
Wang
Bao-en
BE
Zheng
Xin-xiao
XX
Li
Min
M
Mayer
Konstantin
K
Zhang
Shu-wen
SW
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009195:Peroxidase