IL-10 attenuates excessive inflammation in chronic Pseudomonas infection in mice

Cystic fibrosis (CF) lung disease is characterized by an excessive inflamma tory response associated with chronic Pseudomonas aeruginosa endobronchial infection. Compared with bronchoalveolar lavage fluid from healthy subjects , lavage fluid from patients with CF contains elevated proinflammatory cyto kines but negligible amounts of the anti-inflammatory cytokine interleukin- 10 (IL-10). We sought to determine whether IL-10 deficiency results in incr eased local and systemic morbidity in mice with chronic endobronchial infec tion with P. aeruginoso embedded in agar beads and to determine if exogenou s IL-10 might reduce these effects. infected IL-10 knockout mice had more s evere weight loss (p = 0.04) and increased area of lung inflammation (28 +/ - 4 versus 10 +/- 2%, p < 0.002) but no alterations in bacterial burden com pared with wild-type mice. Infected CD-1 mice treated with IL-10 had improv ed survival (p = 0.035), less severe weight loss (p < 0.005), fewer broncho alveolar lavage neutrophils (3 x 10(5)/ml versus 5 x 10(6)/ml, p < 0.02), a nd decreased area of lung inflammation (11 +/- 2 versus 35 +/- 7%, p < 0.01 ) but no alterations in bacterial burden compared with placebo-treated mice . These data suggest that IL-10 is an important regulator of the inflammato ry response to P. aeruginosa endobronchial infection and that further inves tigation into the use of IL-10 in CF is warranted.