Attenuation of lipopolysaccharide-induced acute lung injury by treatment with IL-10.
OBJECTIVE
The aim of this study was to characterize the changes in neutrophils and cytokines in BAL fluid following acute lung injury (ALI), and to determine the protective effect of post-injury treatment with IL-10.


METHODS
A rat model of ALI was established by evenly spraying LPS (16 mg/kg) into the lungs followed by observation for 48 h. Histological changes and the kinetics of neutrophil infiltration were evaluated in the injured lungs. The cytokines (TNF-alpha, IL-6, IL-10 and interferon-gamma) and macrophage-inflammatory protein (MIP-2) were measured in BAL fluid by ELISA. The activation of BAL fluid neutrophils was investigated after treatment with IL-10 in vitro. The protective effect on histology and MIP-2 levels of intra-tracheal instillation of IL-10 12 and 16 h after LPS treatment was studied in vivo.


RESULTS
Intra-tracheal instillation of LPS caused significant lung injury and the activation of neutrophils. The levels of TNF-alpha and IL-6 in BAL fluid peaked at 8 and 16 h after LPS instillation respectively. IL-10 levels reached a maximum at 16-24 h, at the beginning of resolution of tissue injury. IL-10 inhibited the activation of neutrophils in vitro and MIP-2 induction in vivo. IL-10 had a protective effect if it was administered 12 but not 16 h after LPS.


CONCLUSIONS
Neutrophils appeared to play an important role in ALI. Time-dependent treatment with IL-10 after intra-tracheal instillation of LPS was effective in protecting rats from ALI, probably by suppressing pulmonary infiltration with activated neutrophils.
Wu
Chieh-Liang
CL
Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Lin
Liang-Yi
LY
Yang
Jyh-Shyue
JS
Chan
Ming-Cheng
MC
Hsueh
Chi-Mei
CM
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007322:Instillation, Drug; D016753:Interleukin-10 / Q000008:administration & dosage / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea
D016207:Cytokines; D008070:Lipopolysaccharides; D016753:Interleukin-10