Levels Of Interleukin-6 In Bronchoalveolar Lavage Fluid Research Articles

Antibiotic-induced microbiome depletion improves LPS-induced acute lung injury via gut-lung axis

AimsAcute lung injury (ALI) is an acute inflammatory disorder. However, the precise mechanisms underlying the pathology of ALI remain elusive. An increasing evidence suggests the role of the gut-microbiota axis in the pathology of lung injury. This study aimed to investigate whether antibiotic-induced microbiome depletion could affect ALI in mice after lipopolysaccharide (LPS) administration. Main methodsThe effects of antibiotic cocktail (ABX) on ALI in the mice after intratracheally administration of LPS (5 mg/kg) were examined. Furthermore, 16s rRNA analysis and measurement of short-chain fatty acids in feces samples and metabolomics analysis of blood samples were performed. Key findingsLPS significantly increased the interleukin-6 (IL-6) levels in the bronchoalveolar lavage fluid (BALF) of water-treated mice. Interestingly, an ABX significantly attenuated the LPS-induced increase in IL-6 in BALF and lung injury scores. Furthermore, ABX and/or LPS treatment markedly altered the α- and β-diversity of the gut microbiota. There were significant differences in the α- and β-diversity of the water + LPS group and ABX + LPS group. LEfSe analysis identified Enterococusfaecalis, Clostriumtertium, and Bacteroidescaecimyris as potential microbial markers for ABX + LPS group. Untargeted metabolomics analysis identified several plasma metabolites responsible for discriminating water + LPS group from ABX + LPS group. There were correlations between the relative abundance of the microbiome and plasma metabolites. Integrative network analysis showed correlations between IL-6 levels in BALF and several gut microbes (or plasma metabolites). SignificanceThese data suggest that ABX-induced microbiome depletion could protect against LPS-induced ALI via the gut-microbiota-lung axis.

High-mobility group box 1 protein is involved in the protective effect of Saquinavir on ventilation-induced lung injury in mice.

Saquinavir (SQV) is the first FDA approved HIV protease inhibitor. Previous studies showed that SQV can limit Toll-like receptor-4 (TLR4)-mediated inflammatory pathway and nuclear factor-κB (NF-κB) activation, thereby playing a protective role in many kinds of diseases. High-mobility group box 1 (HMGB1) has been identified as an inflammatory mediator and it might express its toxicity in a short period of time in ventilator-induced lung injury (VILI). In this study, C57BL/6 mice were randomly divided into four groups (n = 10): control group and control with SQV group (Con + SQV) were spontaneous breath. HTV group (HTV) received high tidal volume ventilation (HTV) for 4 h. HTV with SQV group (HTV + SQV) were pretreated with 5 mg/kg of SQV for 7 days before HTV. Mice were sacrificed after 4 h of HTV. Lung wet/dry weight (W/D) ratio, alveolar-capillary permeability to Evans blue albumin (EBA), cell counts, total proteins in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level in BALF and lung tissue, and lung histopathology were examined. Our results showed that HTV caused significant lung injury and NF-κB activation, which was correlated with the increase of TNF-α and IL-6 levels in BALF and plasma. SQV pretreatment significantly attenuated pulmonary inflammatory injury, as well as NF-κB activation. These findings indicate that the protective effect of SQV may be associated with the inhibition of NF-κB activation and HMGB1 expression in mice.

Differential effects of long and short carbon nanotubes on the gas-exchange region of the mouse lung

We hypothesise that inflammatory response and morphological characteristics of lung parenchyma differ after exposure to short or long multi-walled carbon nanotubes (MWCNT). Mice were subjected to a single dose of vehicle, short or long MWCNT by pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) obtained at 24 h was analysed for inflammatory reaction and lung tissue was analysed for morphological alterations using stereology. Short MWCNT had stronger potential to induce polymorphonuclear cells whereas long MWCNT increased interleukin-6 levels in BALF. Alveolar septal fibrosis was only observed with short MWCNT. Type II pneumocyte hypertrophy was only detected with long MWCNT. There was no reduction in total alveolar surface area and no sign of type II cell hyperplasia. We observed mild inflammatory and pathological responses to short and long MWCNT in the lung parenchyma depending on the size of the applied MWCNT.

Mild hypothermia attenuates changes in respiratory system mechanics and modifies cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation

Hypothermia was shown to attenuate ventilator-induced lung injury due to large tidal volumes. It is unclear if the protective effect of hypothermia is maintained under less injurious mechanical ventilation in animals without previous lung injury. Tracheostomized rats were randomly allocated to non-ventilated group (group C) or ventilated groups of normothermia (group N) and mild hypothermia (group H). After two hours of mechanical ventilation with inspiratory fraction of oxygen 1.0, respiratory rate 60 min(-1), tidal volume 10 ml x kg(-1), positive end-expiratory pressure (PEEP) 2 cm H2O or immediately after tracheostomy in non-ventilated animals inspiratory pressures were recorded, rats were sacrificed, pressure-volume (PV) curve of respiratory system constructed, bronchoalveolar lavage (BAL) fluid and aortic blood samples obtained. Group N animals exhibited a higher rise in peak inspiratory pressures in comparison to group H animals. Shift of the PV curve to right, higher total protein and interleukin-6 levels in BAL fluid were observed in normothermia animals in comparison with hypothermia animals and non-ventilated controls. Tumor necrosis factor-alpha was lower in the hypothermia group in comparison with normothermia and non-ventilated groups. Mild hypothermia attenuated changes in respiratory system mechanics and modified cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation in animals without previous lung injury.