TNF-α In Bronchoalveolar Lavage Fluid Research Articles

Effect of ciprofloxacin on levels of lipopolysaccharide and cytokines in experimentally induced Gram-negative bacterial pneumonia in mice

This study was performed to examine the ability of ciprofloxacin (CPFX) to suppress the inflammation associated with lipopolysaccharide (LPS) and an inflammatory cytokine in gram-negative bacterial pneumonia. For this purpose we measured viable cell counts in bronchoalveolar lavage fluid (BALF), LPS concentrations in BALF, and BALF levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in mice exposed to Klebsiella pneumoniae. We used three groups of mice: controls, treated with physiological saline; mice treated with CPFX; and mice treated with ceftadizime (CAZ). The viable cell count in BALF was low in both the CAZ and CPFX groups. LPS values in BALF were significantly lower in the CPFX group than in the CAZ group at 48 and 72 h after K. pneumoniae exposure (48 h, P < 0.001; 72 h, P < 0.05). The BALF TNF-alpha level was significantly higher in the CAZ group at 24, 48, and 72 h compared to levels in the control and CPFX groups (P < 0.05). In conclusion, these results suggest that CPFX inhibited increases of LPS and TNF-alpha in gram-negative bacterial pneumonia, thereby suppressing the lung inflammation that accompanies pneumonia.

Effects of cannabinoid receptor ligands on LPS-induced pulmonary inflammation in mice

The effects of cannabinoid receptor agonists WIN 55,212-2, Δ9-tetrahydrocannabinol (Δ9-THC), arachidonoylethanolamide (anandamide) and palmitoylethanolamide on lipopolysaccharide (LPS) -induced bronchopulmonary inflammation in mice were investigated. WIN 55,212-2 and Δ9-THC induced a concentration-dependent decrease in TNF-α level in the bronchoalveolar lavage fluid (BALF) (maximum inhibition 52.7% and 36.9% for intranasal doses of 750 nmol.kg −1 and 2.65 mmol.kg −1, respectively). This effect was accompanied by moderately reduced neutrophil recruitment. Palmitoylethanolamide (750 nmol.kg −1) diminished the level of TNF-α in BALF by 31.5% but had no effect on neutrophil recruitment. Anandamide (7.5–750 nmol.kg-1) did not influence the inflammatory process but TNF-α level and neutrophil recruitment were decreased by 28.0% and 62.0%, respectively, with 0.075 nmol.kg −1. These results demonstrate that the cannabinoid receptor ligands inhibited LPS-induced pulmonary inflammation and suggest that this effect could be at least in part mediated by the cannabinoid CB 2 receptor.

Drugs acting against leukotriene pathways current clinical knowledge

Asthma comprises a triad of reversible airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. Clinical and experimental findings have established eosinophilia as a sign of allergic disorders. In the present investigation, we evaluated the anti-asthmatic effects of schizandrin and its underlying mechanisms in an in vivo murine asthmatic model. To accomplish this, female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and examined for the following typical asthmatic reactions: increased numbers of eosinophils and other inflammatory cells in bronchoalveolar lavage fluid (BALF); production of Th1 cytokines (such as tumor necrosis factor (TNF)-α in BALF); production of Th2 cytokines (such as interleukin IL-4 and IL-5) in BALF; presence of total and OVA-specific immunoglobulins (Ig)E in serum; presence of oxidative stress; hyperplasia of goblet cells in the lung; and marked influx of inflammatory cells into the lung. Our results collectively show that schizandrin exerts profound inhibitory effects on accumulation of eosinophils into the airways and reduces the levels of IL-4, IL-5, IFN-γ, and TNF-α in BALF. Additionally, schizandrin suppresses the production of reactive oxygen species (ROS) in a dose-dependent manner, and inhibits goblet cell hyperplasia and inflammatory cell infiltration in lung tissue. Thus, schizandrin has anti-asthmatic effects, which seem to be partially mediated by reduction of oxidative stress and airway inflammation, in a murine allergic asthma model. These results indicate that schizandrin may be an effective novel therapeutic agent for the treatment of allergic asthma.