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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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Effect of moxifloxacin on IL-1β concentrations in lungs of infected mice. IL-1β concentrations were measured in lungs of moxifloxacin- and saline-treated mice 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). 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 3: Effect of moxifloxacin on IL-1β concentrations in lungs of infected mice. IL-1β concentrations were measured in lungs of moxifloxacin- and saline-treated mice 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). 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: Next, we examined whether a treatment with moxifloxacin modulates the expression of inflammatory mediators in the lung upon bacterial infection. Moxifloxacin per se did not affect the levels of the inflammatory mediators IL-1β (Figure 3), KC (the functional homologue of IL-8 in mice, Figure 4) and IL-17A (Figure 5) in the lungs of mice in the absence of bacterial infection. Concentrations of IL-1β, KC and IL-17A were significantly increased in lungs of mice infected with heat-inactivated and viable P. aeruginosa and S. pneumoniae as compared to the concentrations in lungs of non-infected control mice. Furthermore, infection with viable bacteria induced significantly enhanced expression of these cytokines as compared to infection with heat-inactivated bacteria. Treatment with moxifloxacin resulted in a reduced expression of IL-1β, KC and IL-17A in lungs of mice infected with viable bacteria, whereas the levels of these cytokines in lungs of mice infected with heat-inactivated bacteria were only partially affected by moxifloxacin as compared to saline. IL-β concentrations were reduced in lung homogenates of moxifloxacin-treated mice infected for 6 hours with heat-inactivated P. aeruginosa (Figure 3A) and viable P. aeruginosa (Figure 3D) and in lung homogenates of mice infected with viable S. pneumoniae for 24 hours (Figure 3E). IL-1β could only be detected in BAL fluids from saline-treated mice infected with viable P. aeruginosa (1203 ng/ml ± 126), whereas IL-1β concentrations were below the detection limit in BAL fluids of moxifloxacin-treated mice infected with viable P. aeruginosa and in BAL fluids of mice infected with heat-inactivated bacteria (data not shown). Treatment with moxifloxacin resulted in significantly reduced concentrations of KC in lung homogenates of mice infected with viable P. aeruginosa (Figure 4D) and S. pneumonia (Figure 4E) as compared to saline-treated mice. KC concentrations were also significantly (p < 0.001) reduced in BAL fluids from moxifloxacin-treated mice infected with viable P. aeruginosa (5.4 × 104 ng/ml ± 1533) as compared to infected saline-treated mice (2.1 × 104 ng/ml ± 7507). IL-17A concentrations were significantly reduced in BAL fluids of moxifloxacin-treated mice infected with a high dose of heat-inactivated for 24 hours (Figure 5B) and viable P. aeruginosa (Figure 5C) as compared to the corresponding saline-treated mice. IL-17A was below the detection limit in mice treated with a low dose of inactivated P. aeruginosa for 6 hours (data not shown). Levels of the anti-inflammatory cytokine IL-10 in BAL fluids were below the detection limit (10 pg/ml) in infected and non-infected mice (data not shown). Relative mRNA expression levels of inflammatory mediators were determined in whole lungs of mice infected with inactivated and viable P. aeruginosa for 6 hours. In case of infection with inactivated P. aeruginosa, expression of KC was slightly enhanced in lungs of saline-treated mice compared to moxifloxacin-treated mice (Figure 6A). Infection with viable P. aeruginosa resulted in significantly increased expression levels of KC in lungs of saline-treated mice as compared to moxifloxacin-treated mice (Figure 6B). The expression of IL-β was significantly increased in moxifloxacin-treated mice infected with inactivated and viable P. aeruginosa (Figure 6C and D). No significantly increased levels of expression could be determined for IL-17 6 hours post infection by qRT-PCR (data not shown). In addition, infection with viable P. aeruginosa for 6 hours resulted in an infiltrate of TNF-α-expressing cells into lungs. Figure 7 shows representative hematoxylin/eosin and TNF-α staining of lung sections from areas with strong and moderate cell infiltrates. The infiltrate of TNF-α-expressing cells into lungs of saline-treated mice was significantly increased as compared to moxifloxacin-treated mice (Figure 7C).


Moxifloxacin modulates inflammation during murine pneumonia.

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

Effect of moxifloxacin on IL-1β concentrations in lungs of infected mice. IL-1β concentrations were measured in lungs of moxifloxacin- and saline-treated mice 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). 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

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Figure 3: Effect of moxifloxacin on IL-1β concentrations in lungs of infected mice. IL-1β concentrations were measured in lungs of moxifloxacin- and saline-treated mice 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). 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: Next, we examined whether a treatment with moxifloxacin modulates the expression of inflammatory mediators in the lung upon bacterial infection. Moxifloxacin per se did not affect the levels of the inflammatory mediators IL-1β (Figure 3), KC (the functional homologue of IL-8 in mice, Figure 4) and IL-17A (Figure 5) in the lungs of mice in the absence of bacterial infection. Concentrations of IL-1β, KC and IL-17A were significantly increased in lungs of mice infected with heat-inactivated and viable P. aeruginosa and S. pneumoniae as compared to the concentrations in lungs of non-infected control mice. Furthermore, infection with viable bacteria induced significantly enhanced expression of these cytokines as compared to infection with heat-inactivated bacteria. Treatment with moxifloxacin resulted in a reduced expression of IL-1β, KC and IL-17A in lungs of mice infected with viable bacteria, whereas the levels of these cytokines in lungs of mice infected with heat-inactivated bacteria were only partially affected by moxifloxacin as compared to saline. IL-β concentrations were reduced in lung homogenates of moxifloxacin-treated mice infected for 6 hours with heat-inactivated P. aeruginosa (Figure 3A) and viable P. aeruginosa (Figure 3D) and in lung homogenates of mice infected with viable S. pneumoniae for 24 hours (Figure 3E). IL-1β could only be detected in BAL fluids from saline-treated mice infected with viable P. aeruginosa (1203 ng/ml ± 126), whereas IL-1β concentrations were below the detection limit in BAL fluids of moxifloxacin-treated mice infected with viable P. aeruginosa and in BAL fluids of mice infected with heat-inactivated bacteria (data not shown). Treatment with moxifloxacin resulted in significantly reduced concentrations of KC in lung homogenates of mice infected with viable P. aeruginosa (Figure 4D) and S. pneumonia (Figure 4E) as compared to saline-treated mice. KC concentrations were also significantly (p < 0.001) reduced in BAL fluids from moxifloxacin-treated mice infected with viable P. aeruginosa (5.4 × 104 ng/ml ± 1533) as compared to infected saline-treated mice (2.1 × 104 ng/ml ± 7507). IL-17A concentrations were significantly reduced in BAL fluids of moxifloxacin-treated mice infected with a high dose of heat-inactivated for 24 hours (Figure 5B) and viable P. aeruginosa (Figure 5C) as compared to the corresponding saline-treated mice. IL-17A was below the detection limit in mice treated with a low dose of inactivated P. aeruginosa for 6 hours (data not shown). Levels of the anti-inflammatory cytokine IL-10 in BAL fluids were below the detection limit (10 pg/ml) in infected and non-infected mice (data not shown). Relative mRNA expression levels of inflammatory mediators were determined in whole lungs of mice infected with inactivated and viable P. aeruginosa for 6 hours. In case of infection with inactivated P. aeruginosa, expression of KC was slightly enhanced in lungs of saline-treated mice compared to moxifloxacin-treated mice (Figure 6A). Infection with viable P. aeruginosa resulted in significantly increased expression levels of KC in lungs of saline-treated mice as compared to moxifloxacin-treated mice (Figure 6B). The expression of IL-β was significantly increased in moxifloxacin-treated mice infected with inactivated and viable P. aeruginosa (Figure 6C and D). No significantly increased levels of expression could be determined for IL-17 6 hours post infection by qRT-PCR (data not shown). In addition, infection with viable P. aeruginosa for 6 hours resulted in an infiltrate of TNF-α-expressing cells into lungs. Figure 7 shows representative hematoxylin/eosin and TNF-α staining of lung sections from areas with strong and moderate cell infiltrates. The infiltrate of TNF-α-expressing cells into lungs of saline-treated mice was significantly increased as compared to moxifloxacin-treated mice (Figure 7C).

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