Bronchoalveolar lavage fluid recovered from infected and uninvolved lungs of patients with community-acquired pneumonia (CAP; n=16) on day 6+/-0.8 was analyzed for cytokine, soluble receptor, and antagonist levels. The role of tumor necrosis factor (TNF)-alpha-converting enzyme (TACE) in the resolution of the local inflammatory response was investigated. TNF-alpha, interleukin (IL)-1beta, and IL-6 were elevated in the infected versus uninvolved lobe, whereas IL-10 was not. Epithelial lining fluid (ELF) cytokine levels correlated with intracellular cytokine expression. Levels of proTNF-alpha were reciprocally related to TNF-alpha ELF levels. Levels of soluble receptors, generated by TACE cleavage of membrane-bound precursors, were compartmentalized to infected ELF. TACE was down-regulated by internalization in cells from the site of infection. These data demonstrate that, in vivo during CAP, TACE has a role in regulating resolution of the local inflammatory response by modulating levels of pro- and counterinflammatory mediators.
Royal College of Surgeons in Ireland ->