Airway inflammation is a common feature of infectious pulmonary diseases

Conclusions: We have provided evidence that TEL exerts potent antiinflammatory effects in LPS-induced airways injury. We propose that TEL acts in the early phase of inflammation by reducing the release of inflammatory mediators through NF-kB inhibition, and in the later phase through enhancement of inflammatory cell apoptosis.

Key words: airway inflammation; antiinflammatory activity; apoptosis; macrophage inflammatory protein-2; neutrophil recruitment; nuclear factor-KB inhibition; telithromycin

Abbreviations: DMEM = Dulbecco modified essential medium; FCS = fetal calf serum; iNOS = inducible nitric oxide synthase; IP = intraperitoneal; LPS = lipopolysaccharide; MIP = macrophage inflammatory protein; MLE = murine lung epithelial; NF = nuclear factor; NO = nitric oxide; PBS = phosphate-buffered saline; TEL = telithromycin; TNF = tumor necrosis factor

Airway inflammation is a common feature of infectious pulmonary diseases. Although the inflammatory response clearly contributes to the reduction of the number of pathogens obtained from the site of infection, a prolonged inflammatory response might worsen lung injury. Alveolar macrophages are the first line of innate cell-mediated immunity in the lower respiratory tract. The lipopolysaccharide (LPS) produced by Gram-negative bacteria is an important inducer of lung injury. Through the activation of the transcription factor nuclear factor (NF)-kB, LPS causes the release by macrophages of inflammatory mediators such as tumor necrosis factor (TNF)-a and chemokines, and the expression of inducible nitric oxide synthase (iNOS) Although alveolar macrophages are considered to be responsible for initiating the inflammatory cascade in the lung, the airway epithelial NF-kB activation is sufficient to promote neutrophilic airway inflammation.

Telithromycin (TEL) belongs to the ketolide family, which is a new class of 14-membered ring macrolide agents that are characterized by a keto group at position 3 of the macrolide ring. TEL is active against bacteria causing community-acquired pneumonia, acute exacerbation of chronic bronchitis, and acute sinusitis. TEL exerts immunomodulatory effects in vitro and in experimental models of septic shock, but there have been no studies evaluating the activity of TEL in LPS-induced airway inflammation in mice.

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