TL Bonfield, JR Panuska, MW Konstan, KA Hilliard, JB Hilliard, H Ghnaim and M Berger
Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.

Chronic pulmonary infection with Pseudomonas aeruginosa continues to be the major cause of morbidity and mortality in cystic fibrosis (CF). Several characteristics of CF, including the excessive influx of neutrophils into the airways, cachexia, and hyperglobulinemia, could reflect the effects of cytokines, such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor (TNF-alpha). We hypothesized that these pro-inflammatory cytokines, produced by alveolar macrophages in response to pseudomonas and/or other microorganisms, promote the destructive inflammatory process in the lung. We evaluated bronchoalveolar lavage (BAL) fluid and BAL macrophages from 22 CF patients and 13 healthy control (HC) subjects, measuring soluble TNF- alpha, IL-1 beta, IL-6, and IL-8 and the regulatory molecules TNF soluble receptor (TNF-sR), IL-1 receptor antagonist (IL-1Ra), and IL-10 (cytokine synthesis inhibitory factor). Levels of the proinflammatory cytokines were higher in CF versus HC BAL (p < or = 0.05 for IL-1, TNF, and IL-8; p = 0.06 for IL-6). In contrast, HC BAL contained significantly more IL-10 than CF BAL (p < 0.05), but TNF-sR and IL-1Ra were similar. Immunocytochemistry demonstrated a higher percentage of CF than control BAL macrophages expressing intracellular cytokines (p < 0.05). Thus, enhanced macrophage production of proinflammatory cytokines and decreased production of the regulatory molecule IL-10 may have important roles in the pathogenesis of CF lung disease.

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