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Moxifloxacin modulates inflammation during murine pneumonia.

Beisswenger C, Honecker A, Kamyschnikow A, Bischoff M, Tschernig T, Bals R - Respir. Res. (2014)

Bottom Line: Alveolar cells were determined in bronchoalveolar lavage fluits.The inflammation was increased after the inoculation of viable bacteria compared to inactivated bacteria.These data show that in this pneumonia model moxifloxacin has anti-inflammatory properties beyond its antibacterial activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine V - Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany. christoph.beisswenger@uks.eu.

ABSTRACT

Background: Moxifloxacin is a synthetic antibacterial agent belonging to the fluoroquinolone family. The antimicrobial activity of quinolones against Gram-positive and Gram-negative bacteria is based on their ability to inhibit topoisomerases. Quinolones are described to have immunomodulatory features in addition to their antimicrobial activities. It was the goal of this study to examine whether a short term treatment with moxifloxacin modulates the inflammation during a subsequently induced bacterial infection in an animal model.

Methods: Mice were treated with moxifloxacin or saline for two consecutive days and were subsequently intranasally infected with viable or heat-inactivated bacterial pathogens (Streptococcus pneumoniae, Pseudomonas aeruginosa) for 6 and 24 hours. Measurements of cytokines in the lungs and plasma were performed. Alveolar cells were determined in bronchoalveolar lavage fluits.

Results: The inflammation was increased after the inoculation of viable bacteria compared to inactivated bacteria. Numbers of total immune cells and neutrophils and concentrations of inflammatory mediators (e.g. KC, IL-1β, IL-17A) were significantly reduced in lungs of moxifloxacin-treated mice infected with inactivated and viable bacterial pathogens as compared to infected control mice. Plasma concentrations of inflammatory mediators were significantly reduced in moxifloxacin-treated mice. Immunohistochemistry showed a stronger infiltrate of TNF-α-expressing cells into lungs of saline-treated mice infected with viable P. aeruginosa as compared to moxifloxacin-treated mice.

Conclusions: These data show that in this pneumonia model moxifloxacin has anti-inflammatory properties beyond its antibacterial activity.

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Related in: MedlinePlus

Moxifloxacin treatment results in a reduced influx of immune cells into the lung during bacterial pneumonia. BAL fluids of moxifloxacin- and saline-treated mice were collected 6 or 24 h post intranasal infection with heat-inactivated P. aeruginosa(A/B/C), viable P. aeruginosa(D), and heat-inactivated or viable S. pneumoniae(E). Total cell numbers were determined. Data are shown as mean ± SEM. Bars indicate significant differences of *p < 0.05, **p < 0.01, and ***p < 0.001, (n ≥ 5 for each group).
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Figure 1: Moxifloxacin treatment results in a reduced influx of immune cells into the lung during bacterial pneumonia. BAL fluids of moxifloxacin- and saline-treated mice were collected 6 or 24 h post intranasal infection with heat-inactivated P. aeruginosa(A/B/C), viable P. aeruginosa(D), and heat-inactivated or viable S. pneumoniae(E). Total cell numbers were determined. Data are shown as mean ± SEM. Bars indicate significant differences of *p < 0.05, **p < 0.01, and ***p < 0.001, (n ≥ 5 for each group).

Mentions: Moxifloxacin treatment did not affect the levels of total immune cells (Figure 1) and neutrophils (Figure 2) in the lungs of mice in the absence of bacterial infection. Infection with heat-inactivated and viable bacteria resulted in a neutrophil-dominated inflammatory response in the lung. The infection with heat-inactivated and viable P. aeruginosa and S. pneumoniae led to enhanced numbers of total immune cells (Figure 1) and neutrophils (Figure 2) in BAL fluids 6 and 24 hours post infection as compared to non-infected control groups. Furthermore, in the case of S. pneumoniae, viable bacteria induced a significantly enhanced influx of total immune cells (Figure 1E) and neutrophils (Figure 2E) into lungs as compared to heat-inactivated S. pneumoniae. Interestingly, treatment with moxifloxacin affected the levels of total immune cells and neutrophils in the lungs of mice infected with viable and heat-inactivated bacteria. Treatment with moxifloxacin, as compared to saline, resulted in significantly reduced levels of total immune cells (Figure 1A to C) and neutrophils (Figure 2A to C) in BAL fluids of mice infected with a low dose or a high dose of heat-inactivated P. aeruginosa or with viable S. pneumoniae (Figures 1E and 2E). There was no difference in the numbers of total immune cells in BAL fluids between moxifloxacin- and saline-treated mice infected with viable P. aeruginosa (Figures 1D and 2D). Levels of macrophages and lymphocytes in BAL fluids were not affected by treatment with moxifloxacin (data not shown).


Moxifloxacin modulates inflammation during murine pneumonia.

Beisswenger C, Honecker A, Kamyschnikow A, Bischoff M, Tschernig T, Bals R - Respir. Res. (2014)

Moxifloxacin treatment results in a reduced influx of immune cells into the lung during bacterial pneumonia. BAL fluids of moxifloxacin- and saline-treated mice were collected 6 or 24 h post intranasal infection with heat-inactivated P. aeruginosa(A/B/C), viable P. aeruginosa(D), and heat-inactivated or viable S. pneumoniae(E). Total cell numbers were determined. Data are shown as mean ± SEM. Bars indicate significant differences of *p < 0.05, **p < 0.01, and ***p < 0.001, (n ≥ 5 for each group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4118268&req=5

Figure 1: Moxifloxacin treatment results in a reduced influx of immune cells into the lung during bacterial pneumonia. BAL fluids of moxifloxacin- and saline-treated mice were collected 6 or 24 h post intranasal infection with heat-inactivated P. aeruginosa(A/B/C), viable P. aeruginosa(D), and heat-inactivated or viable S. pneumoniae(E). Total cell numbers were determined. Data are shown as mean ± SEM. Bars indicate significant differences of *p < 0.05, **p < 0.01, and ***p < 0.001, (n ≥ 5 for each group).
Mentions: Moxifloxacin treatment did not affect the levels of total immune cells (Figure 1) and neutrophils (Figure 2) in the lungs of mice in the absence of bacterial infection. Infection with heat-inactivated and viable bacteria resulted in a neutrophil-dominated inflammatory response in the lung. The infection with heat-inactivated and viable P. aeruginosa and S. pneumoniae led to enhanced numbers of total immune cells (Figure 1) and neutrophils (Figure 2) in BAL fluids 6 and 24 hours post infection as compared to non-infected control groups. Furthermore, in the case of S. pneumoniae, viable bacteria induced a significantly enhanced influx of total immune cells (Figure 1E) and neutrophils (Figure 2E) into lungs as compared to heat-inactivated S. pneumoniae. Interestingly, treatment with moxifloxacin affected the levels of total immune cells and neutrophils in the lungs of mice infected with viable and heat-inactivated bacteria. Treatment with moxifloxacin, as compared to saline, resulted in significantly reduced levels of total immune cells (Figure 1A to C) and neutrophils (Figure 2A to C) in BAL fluids of mice infected with a low dose or a high dose of heat-inactivated P. aeruginosa or with viable S. pneumoniae (Figures 1E and 2E). There was no difference in the numbers of total immune cells in BAL fluids between moxifloxacin- and saline-treated mice infected with viable P. aeruginosa (Figures 1D and 2D). Levels of macrophages and lymphocytes in BAL fluids were not affected by treatment with moxifloxacin (data not shown).

Bottom Line: Alveolar cells were determined in bronchoalveolar lavage fluits.The inflammation was increased after the inoculation of viable bacteria compared to inactivated bacteria.These data show that in this pneumonia model moxifloxacin has anti-inflammatory properties beyond its antibacterial activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine V - Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany. christoph.beisswenger@uks.eu.

ABSTRACT

Background: Moxifloxacin is a synthetic antibacterial agent belonging to the fluoroquinolone family. The antimicrobial activity of quinolones against Gram-positive and Gram-negative bacteria is based on their ability to inhibit topoisomerases. Quinolones are described to have immunomodulatory features in addition to their antimicrobial activities. It was the goal of this study to examine whether a short term treatment with moxifloxacin modulates the inflammation during a subsequently induced bacterial infection in an animal model.

Methods: Mice were treated with moxifloxacin or saline for two consecutive days and were subsequently intranasally infected with viable or heat-inactivated bacterial pathogens (Streptococcus pneumoniae, Pseudomonas aeruginosa) for 6 and 24 hours. Measurements of cytokines in the lungs and plasma were performed. Alveolar cells were determined in bronchoalveolar lavage fluits.

Results: The inflammation was increased after the inoculation of viable bacteria compared to inactivated bacteria. Numbers of total immune cells and neutrophils and concentrations of inflammatory mediators (e.g. KC, IL-1β, IL-17A) were significantly reduced in lungs of moxifloxacin-treated mice infected with inactivated and viable bacterial pathogens as compared to infected control mice. Plasma concentrations of inflammatory mediators were significantly reduced in moxifloxacin-treated mice. Immunohistochemistry showed a stronger infiltrate of TNF-α-expressing cells into lungs of saline-treated mice infected with viable P. aeruginosa as compared to moxifloxacin-treated mice.

Conclusions: These data show that in this pneumonia model moxifloxacin has anti-inflammatory properties beyond its antibacterial activity.

Show MeSH
Related in: MedlinePlus