Rauchen supprimiert das angeborene Immunsystem

Background: Smoking increases the susceptibility to pulmonary infection and is a risk factor for the development of chronic obstructive pulmonary disease (COPD). We postulated that cigarette smoke (CS) suppresses the activation of the innate immune system in response to bacterial infection. Methods: With sensitive ex-vivo analysis we measured the level of the endogenous antibiotic peptide human beta-defensin-2 (hBD-2) in pharyngeal washing fluids and sputum of patients with community acquired pneumonia. The regulation of antibacterial host defense molecules was studied in vitro. The effect of CS on the antibacterial activity of differentiated airway epithelium and the expression of host defense molecules was studied in an infection model in vitro. Results: Current or former smoking was associated with significantly reduced hBD-2 levels in pharyngeal washing fluid and sputum from patients with acute pneumonia. Exposure of airway epithelium to smoke in vitro inhibited the induction of hBD-2 by bacteria. This correlated with decreased antimicrobial activity and concentration of hBD-2. Katalase as an antioxidant enzyme was able to restore the expression of hBD-2 after CS exposure and bacterial stimulation in part. After bacterial stimulation also increased concentrations of the cytokine IL-6 and the chemokine IL-8 were measured. The expression of theses cytokines was not influenced by CS exposure. Since hBD-2 and IL-6 or IL-8 are NF-kB dependent proteins, the activation of the canonical NF-kB pathway after cigarette exposure and bacterial stimualtion was investigated. After bacterial stimualtion a clear nuclear localization and activation of p65 was measured, that was abrogated by previous CS exposure. CS contains numerous reactive and toxic components and it is known that cellular stress may interfere with the activation of p65. CS exposure induces the expression of heat shock protein-70 (Hsp-70), -90a (Hsp-90a) and -90b (Hsp-90b). The expression of Hsp-70 could be reduced by treatment with Katalase, that correlates with the increased hBD-2 expression. Conclusion: Smoke exposure suppresses the induction of epithelial antibacterial host defenses. These findings directly link smoking with increased susceptibility to infection. The underlaying mechanimsms may be the reduced expression of hBD-2 due to a suppressed activation of p65. The reduced expression of p65 may be caused by increased oxidative and cellular stress induced by chemicals from cigarette smoke. This mechanism may be important in the pathogenesis of pneumonia and COPD.