Intrapulmonary concentrations of inflammatory cytokines in a mouse model of chronic respiratory infection caused by Pseudomonas aeruginosa

We investigated the role of inflammatory cytokines in a mouse model of chro nic Pseudomonas aeruginosa infection mimicking diffuse panbronchiolitis (DP B), and determined the effects of clarithromycin therapy on the production of these cytokines. The concentrations of IL-1 beta, IL-2, LL-4, IL-5, inte rferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were measured serially in the lungs of mice with experimentally induced chronic respiratory P. aeruginosa infection until 60 days after inoculation. The co ncentrations of these cytokines during the course of the disease were signi ficantly higher than baseline (before inoculation, P < 0.01 for all cytokin es). Clarithromycin significantly inhibited the production of IL-1 beta and TNF-alpha in the lung (P < 0.01). The same treatment also reduced the leve ls of other cytokines, albeit insignificantly. Treatment with anti-TNF-alph a antibody significantly reduced the number of pulmonary lymphocytes and co ncentration of IL-1 beta in the lung (P < 0.01), but did not change the num ber of viable bacteria. Our findings resemble those detected in bronchoalve olar lavage fluid of patients with DPB and indicate that inflammatory cytok ines play an important role in chronic P. aeruginosa lung infection. Our re sults also show that macrolides modulated the production of these cytokines , ultimately reducing lymphocyte accumulation in the lung. Our data suggest that anti-TNF-alpha antibody might be a useful new strategy for the treatm ent of chronic respiratory P. aeruginosa infection.