Clarithromycin Prevents Smoke-induced Emphysema in Mice

Nakanishi, Yoshinobu; Kobayashi, Dale K.; Asano, Yasuo; Sakurai, Takanobu; Kashimura, Masato; Okuyama, Shigeru; Yoneda, Yukio; Shapiro, Steven D.; Takayama, Kiyoshi

doi:10.1164/rccm.200806-905oc

Cited by 44 publications

(32 citation statements)

References 40 publications

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“…Recently phosphodiesterase 4 inhibitors and some other agents as prostacyclin analog and clarithromycin have been reported to prevent emphysema in animals exposed to cigarette smoke (Chen et al, 2009;Mori et al, 2008;Nakanishi et al, 2009) but nothing is known about bronchodilators and the involved mechanisms still remain to be explored. The actions of these drugs upon the sub-acute or chronic phase of the inflammatory process are poorly documented.…”

Section: Discussionmentioning

confidence: 99%

Effects of formoterol and ipratropium bromide on repeated cadmium inhalation-induced pulmonary inflammation and emphysema in rats

Zhang

Fiévez

Zhang

et al. 2010

European Journal of Pharmacology

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The anti-inflammatory properties of inhaled formoterol and ipratropium bromide, alone or in combination, were investigated in a rat model of chronic pulmonary inflammation with airspace enlargement induced by cadmium inhalation. At the end of the protocol, cadmium-induced increase of airway resistance was prevented by formoterol (4 mg/30 ml) or ipratropium (0.20 mg/20 ml). Formoterol elicited a significant decrease in total cell and neutrophil counts in bronchoalveolar lavage fluid as well as on the activity of gelatinase B (MMP-9), an enzyme strongly expressed in alveolar macrophages and epithelial cells. Additionally, a significant attenuation of the lung lesions characterized by inflammatory cell infiltration within the alveoli and the interstitium and a decrease in mean linear intercept were observed. Although ipratropium alone had no effects on the cadmium-induced pulmonary inflammation and emphysema, its combination with an inefficient concentration of formoterol (1 mg/30 ml) showed a synergistic inhibitory effect on neutrophil and total cell counts as well as on the mean linear intercept associated with a synergistic inhibition on the MMP-9 activity. Gelatinase A (MMP-2) activity was not influenced by drug pretreatments. Neither macrophage metalloelastase (MMP-12) activity nor levels of cytokines IL-1β, TNF-α and GM-CSF in bronchoalveolar lavage fluid were modified in rats chronically exposed to cadmium. No desensitization of β 2 -adrenoceptors or cholinergic receptors on airway smooth muscles and inflammatory cells during the protocol was observed. In conclusion, formoterol alone or combined with ipratropium bromide partially protects the lungs against the chronic inflammation and airspace enlargement by reducing neutrophilic infiltration possibly via the inhibition of MMP-9 activity.

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Section: Discussionmentioning

confidence: 99%

Effects of formoterol and ipratropium bromide on repeated cadmium inhalation-induced pulmonary inflammation and emphysema in rats

Zhang

Fiévez

Zhang

et al. 2010

European Journal of Pharmacology

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“…Animal models provided further evidence that macrolides may block the proinflammatory actions of LPS on the airway [119] and ameliorate emphysema induced by cigarette smoke in mice in a manner that is independent of antibiotic effects [120].…”

Section: Macrolidesmentioning

confidence: 99%

Emerging anti-inflammatory strategies for COPD

et al. 2012

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The hallmark of chronic obstructive pulmonary disease (COPD) is an enhanced or abnormal inflammatory immune response of the lungs to inhaled particles and gases, usually from cigarette smoke, characterised by increased numbers of neutrophils, activated macrophages and activated T-lymphocytes (Tc1 and Th1 cells). Therefore, suppression of the inflammatory response is a logical approach to the treatment of COPD. Despite the inflammatory nature of COPD, currently available anti-inflammatory therapies provide little or no benefit in COPD patients and may have detrimental effects. For this reason, there is an urgent need to discover effective and safe anti-inflammatory treatments that might prevent the relentless progression of the disease. In recent years, attention has largely been focused on inhibition of recruitment and activation of inflammatory cells, and on antagonism of their products. In this review, we put together a summary of the state-of-the-art development of clearly and/or potentially useful anti-inflammatory strategies in COPD.

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“…There have been few trials examining the efficacy of this, however a meta-analysis of 9 trials suggested that antibiotics reduced the days of illness experienced due to exacerbations of chronic bronchitis, without reducing actual exacerbation frequency (178). Erythromycin has been shown to reduce exacerbation frequency in patients with chronic bronchitis and COPD (179) and clarithromycin has been shown to reduce the development of emphysema in smokeexposed mice (180). These actions are thought to be mediated via the macrolides effect on matrix metalloproteinase 9 secretion (a proteinase) and are separate from the anti-microbial properties of the drugs (181).…”

Section: Treatments For Stable Diseasementioning

confidence: 99%