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.CONCLUSION: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.