Current Concepts: Infection in the Pathogenesis and Course of Chronic Obstructive Pulmonary Disease
Division of Pulmonary and Critical Medicine, Department of Medicine, University at Buffalo, State University of New York, and Department of Veterans Affairs Western New York Healthcare System, Buffalo 14215, USA. New England Journal of Medicine
(Impact Factor: 55.87).
12/2008; 359(22):2355-65. DOI: 10.1056/NEJMra0800353
New molecular, cellular, and immunologic techniques used to study host-pathogen interactions have led to a reexamination of the role of infection in chronic obstructive pulmonary disease (COPD). There is now considerable evidence that infection plays a major role in the pathogenesis and clinical course of COPD. A vicious circle of infection and inflammation is thought to lead to exacerbations of the disease.
Available from: Olivier Le Rouzic
- "Acute exacerbation of COPD patients is associated with a greater decline in lung function, enhanced oedema as well as airway and systemic inflammation (Agusti et al., 2003). Among major bacterial species causing COPD exacerbation are Streptococcus pneumoniae, nontypeable Haemophilus influenzae and Moraxella catarrhalis (Sethi and Murphy, 2008). Cigarette smoking is associated with diminished antibacterial immune responses and delayed clearance of microbial agents (Drannik et al., 2004). "
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ABSTRACT: Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation.
Available from: Sanjay H Chotirmall
- "" Inflamm-aging " often takes place and is associated with immunosuppression and low grade inflammation . When secondary pulmonary infection occurs as a result of impaired host response, secondary inflammation develops . "
Available from: Anja Honecker
- "Acute and chronic inflammation and infection of the lung also contribute to tissue destruction and loss of lung function in COPD and CF [1,5]. Bacterial and viral infections are associated with exacerbations of COPD [1,6]. In CF, ongoing inflammation and activation of immune mechanisms is evoked by colonizing bacteria, such as P. aeruginosa. "
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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.
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.
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.
These data show that in this pneumonia model moxifloxacin has anti-inflammatory properties beyond its antibacterial activity.
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