Ceftiofur attenuates lipopolysaccharide-induced acute lung injury.

Ceftiofur is a new broad-spectrum, third-generation cephalosporin antibiotic for veterinary use. Our laboratory has previously been reported that ceftiofur can modulate early cytokine responses and increase mouse survival in endotoxemia. In the present study, we investigated the effect of ceftiofur on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in vivo. Mice were pretreated with ceftiofur 1h before challenge with a dose of 0.5mg/kg LPS. Mice treated with LPS alone showed marked increased TNF-alpha, IL-6, and IL-8 levels in the bronchoalveolar lavage fluid (BALF). When pretreated with 30mg/kg of ceftiofur, the TNF-alpha, IL-6, and IL-8 levels were significantly decreased. In addition, the W/D ratio of the lung tissue and the number of total cells, neutrophils and macrophages in the BALF significantly decreased at 8h after pretreatment with ceftiofur. Furthermore, ceftiofur markedly attenuated the LPS-induced histological alteration. These studies indicate that ceftiofur significantly decreases the inflammation in a murine model of LPS-mediated ALI and may represent a novel prevention strategy for nonspecific inflammation in the lungs.

Chu X ，Song K ，Xu K ，Zhang X ，Zhang X ，Song Y ，Wang D ，Liu S ，Deng X ... -  《-》

Protective effect of florfenicol on acute lung injury induced by lipopolysaccharide in mice.

Zhang X ，Song K ，Xiong H ，Li H ，Chu X ，Deng X ... -  《-》

Taraxacum officinale protects against lipopolysaccharide-induced acute lung injury in mice.

Taraxacum officinale has been frequently used as a remedy for inflammatory diseases. In the present study, we investigated the in vivo protective effect of Taraxacum officinale on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Taraxacum officinale at 2.5, 5 and 10 mg/kg was orally administered once per day for 5 days consecutively, followed by 500 microg/kg LPS was instilled intranasally. The lung wet/dry weight (W/D) ratio, protein concentration and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) were determined. Superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities, and histological change in the lungs were examined. The levels of inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the BALF were measured using ELISA. We found that Taraxacum officinale decreased the lung W/D ratio, protein concentration and the number of neutrophils in the BALF at 24 h after LPS challenge. Taraxacum officinale decreased LPS-induced MPO activity and increased SOD activity in the lungs. In addition, histopathological examination indicated that Taraxacum officinale attenuated tissue injury of the lungs in LPS-induced ALI. Furthermore, Taraxacum officinale also inhibited the production of inflammatory cytokines TNF-alpha and IL-6 in the BALF at 6h after LPS challenge in a dose-dependent manner. These results suggest that Taraxacum officinale protects against LPS-induced ALI in mice.

Liu L ，Xiong H ，Ping J ，Ju Y ，Zhang X ... -  《-》

[The effect of recombinant interleukin-10/Fc fusion protein on lipopolysaccharide-induced acute lung injury in mice].

Bi MH ，Wang BE ，Zheng XX ，Li M ，Mayer K ，Zhang SW ... -  《-》

Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models.

Isoforskolin was isolated from Coleus forskohlii native to Yunnan in China. We hypothesize that isoforskolin pretreatment attenuates acute lung injury induced by lipopolysaccharide (endotoxin). Three acute lung injury models were used: situ perfused rat lung, rat and mouse models of endotoxic shock. Additionally, lipopolysaccharide stimulated proinflammatory cytokine production was evaluated in human mononuclear leukocyte. In situ perfused rat lungs, pre-perfusion with isoforskolin (100, and 200 μM) and dexamethasone (65 μM, positive control) inhibited lipopolysaccharide (10 mg/L) induced increases in lung neutrophil adhesion rate, myeloperoxidase activity, lung weight Wet/Dry ratio, permeability-surface area product value, and tumor necrosis factor (TNF)-α levels. In rats, pretreatments with isoforskolin (5, 10, and 20 mg/kg, i.p.) and dexamethasone (5mg/kg, i.p.) markedly reduced lipopolysaccharide (6 mg/kg i.v.) induced increases of karyocyte, neutrophil counts and protein content in bronchoalveolar lavage fluid, and plasma myeloperoxidase activity. Lung histopathology showed that morphologic changes induced by lipopolysaccharide were less pronounced in the isoforskolin and dexamethasone pretreated rats. In mice, 5 mg/kg isoforskolin and dexamethasone caused 100% and 80% survival, respectively, after administration of lipopolysaccharide (62.5mg/kg, i.v., 40% survival if untreated). In human mononuclear leukocyte, isoforskolin (50, 100, and 200 μM) and dexamethasone (10 μM) pre-incubation lowered lipopolysaccharide (2 μg/mL) induced secretion of the cytokine TNF-α, and interleukins (IL)-1β, IL-6, and IL-8. In conclusion, pretreatment with isoforskolin attenuates lipopolysaccharide-induced acute lung injury in several models, and it is involved in down-regulation of inflammatory responses and proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8.

Yang W ，Qiang D ，Zhang M ，Ma L ，Zhang Y ，Qing C ，Xu Y ，Zhen C ，Liu J ，Chen YH ... -  《-》