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Immunomodulatory effects of macrolides during community-acquired pneumonia: a literature review
Journal of Antimicrobial Chemotherapy, 2011
Macrolides are known to possess immunomodulatory properties, next to their antimicrobial effects. These immunomodulatory activities have been proven beneficial in chronic pulmonary inflammatory diseases. Whether macrolides also exert favourable immunomodulatory effects during acute inflammation, and therefore can act as adjuvant therapy in community-acquired pneumonia (CAP), is less clear. We aimed to give an overview of the existing evidence from in vitro and in vivo studies on the immunomodulatory effects of macrolides during CAP. A comprehensive search in the PubMed/MEDLINE and Embase databases was performed. Two investigators independently examined the eligible literature. Studies that dealt with the effects of macrolides on the immune response, in terms of cytokine secretion and the number or function of inflammatory and structural cells during acute inflammation, were included. A total of 27 studies were included, of which 15 were in vitro studies, 9 in vivo, 2 both in vivo and in vitro, and 1 was in human subjects. Although the methods and experimental model systems used in these studies are very heterogeneous, macrolides in general tempered inflammation caused by viable and non-viable bacteria or their products. Cytokine secretion decreased, as did inflammatory and structural cell activation and histological inflammatory signs. Not all data, however, are consistent and sometimes pro-inflammatory effects were found. To conclude, the available literature suggests that macrolides can temper the inflammatory response during CAP, independent of their antimicrobial activity. However, because the studies differ in their methodology, no definite conclusions can be drawn.
Antimicrobial Agents and Chemotherapy, 2009
Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against M. pneumoniae . We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of M. pneumoniae pneumonia. BALB/c mice were inoculated intranasally with M. pneumoniae and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], interleukin 1β [IL-1β], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1α, MIG, KC, MCP-1, and IP-10). BAL M. pneumoniae concentrations in mice treated with tigecycline...
Treatment of experimental chronic pulmonary mycoplasmosis
International Journal of Antimicrobial Agents, 2006
Mycoplasma pneumoniae infection has been associated with chronic lung disease. Treatment of chronic pulmonary mycoplasmosis has not been well investigated. BALB/c mice were intranasally inoculated once with M. pneumoniae or with sterile media (uninfected controls). Infected mice were treated with telithromycin or placebo daily for 10 days in the chronic phase of disease (18 months after inoculation). Mice (n = 43) were evaluated before therapy and 1 day after completion of telithromycin. Treatment of infected mice with telithromycin at 18 months after infection significantly reduced chronic pulmonary histological inflammation compared with infected mice given placebo; however, this treatment did not improve airway obstruction or airway hyperresponsiveness. Therapy longer than 10 days may be necessary to improve pulmonary function.
Antimicrobial Agents and Chemotherapy, 2003
Because macrolide antibiotics are hypothesized to possess immunomodulatory activity independent of their antimicrobial activity, we evaluated the immunomodulatory effect of clarithromycin in a murine model of lung inflammation induced by either live or UV-killed Mycoplasma pneumoniae. BALB/c mice were intranasally inoculated once with live or UV-killed M. pneumoniae. Clarithromycin (25 mg/kg of body weight) or placebo was subcutaneously administered once daily in both groups of mice. In mice infected with live M. pneumoniae, clarithromycin treatment significantly reduced quantitative M. pneumoniae bronchoalveolar lavage (BAL) culture, pulmonary histopathologic scores (HPS), and airway resistance-obstruction (as measured by plethysmography) compared with placebo. Concentrations of tumor necrosis factor alpha, gamma interferon, interleukin-6 (IL-6), mouse KC (functional IL-8), JE/MCP-1, and MIP-1␣ in BAL fluid were also significantly decreased in mice infected with live M. pneumoniae given clarithromycin. In contrast, mice inoculated with UVkilled M. pneumoniae had no significant reduction in HPS, airway resistance-obstruction, or BAL cytokine or chemokine concentrations in response to clarithromycin administration. Clarithromycin therapy demonstrated beneficial effects (microbiologic, histologic, respiratory, and immunologic) on pneumonia in the mice infected with live M. pneumoniae; this was not observed in the mice inoculated with UV-killed M. pneumoniae.
Infection and Immunity, 2001
Because Mycoplasma pneumoniae is hypothesized to play an important role in reactive airway disease/asthma, a comprehensive murine model of M. pneumoniae lower respiratory infection was established. BALB/c mice were intranasally inoculated once withM. pneumoniae and sacrificed at 0 to 42 days postinoculation. All mice became infected and developed histologic evidence of acute pulmonary inflammation, which cleared by 28 days postinoculation. By contrast, M. pneumoniae persisted in the respiratory tract for the entire 42 days studied. Tumor necrosis factor alpha, gamma interferon, interleukin-6 (IL-6), KC (functional IL-8), MIP-1α, and MCP-1/JE concentrations were significantly elevated in bronchoalveolar lavage samples, whereas IL-4 and IL-10 concentrations were not significantly elevated. Pulmonary airflow resistance, as measured by plethysmography, was detected 1 day postinoculation and persisted even after pulmonary inflammation had resolved at day 28. Serum anti-M. pneumoniae immu...
Mycoplasma pneumoniae Induces Host-Dependent Pulmonary Inflammation and Airway Obstruction in Mice
American Journal of Respiratory Cell and Molecular Biology, 2005
Respiratory tract infections result in wheezing in a subset of patients. Mycoplasma pneumoniae is a common etiologic agent of acute respiratory infection in children and adults that has been associated with wheezing in 20-40% of individuals. The current study was undertaken to elucidate the host-dependent pulmonary and immunologic response to M. pneumoniae respiratory infection by studying mice with different immunogenetic backgrounds (BALB/c mice versus C57BL/6 mice). After M. pneumoniae infection, only BALB/c mice developed significant airway obstruction (AO) compared with controls. M. pneumoniae-infected BALB/c mice manifested significantly elevated airway hyperresponsiveness (AHR) compared with C57BL/6 mice 4 and 7 d after inoculation as well as BALB/c control mice. Compared with C57BL/6 mice, BALB/c mice developed worse pulmonary inflammation, including greater peribronchial infiltrates. Infected BALB/c mice had significantly higher concentrations of tumor necrosis factor-␣, interferon-␥, interleukin (IL)-1, IL-6, IL-12, KC (functional IL-8), and macrophage inflammatory protein 1␣ in the bronchoalveolar lavage fluid compared with infected C57BL/6 mice. No differences in IL-2, IL-4, IL-5, IL-10, and granulocyte/macrophage colony-stimulating factor concentrations were found. The mice in this study exhibited host-dependent infection-related AO and AHR associated with chemokine and T-helper type (Th)1 pulmonary host response and not Th2 response after M. pneumoniae infection.
Antimicrobial Agents and Chemotherapy, 2004
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