Cytokines and inflammatory mediators do not indicate acute infection in cystic fibrosis

Various treatment regimens and difficulties with research design are encoun tered with cystic fibrosis (CF) because no standard diagnostic criteria exi st for defining acute respiratory exacerbations. This study evaluated the r ole of serial monitoring of concentrations of selected cytokines and inflam matory mediators in serum and sputum as predictors of respiratory exacerbat ion, as useful outcome measures for CF, and to guide therapy. Interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-ol), neutrophil elastase-ol-l-pro tease inhibitor complex (NE complex), protein, and alpha-1-protease inhibit or (alpha-1-PI) were measured in serum and sputum collected from CF patient s during respiratory exacerbations and periods of well-being. Levels of NE complex, protein, and alpha-1-PI in sputum rose during respiratory exacerba tions and fell after institution of antibiotic therapy (P = 0.078, 0.001, a nd 0.002, respectively). Mean (+/- standard error of the mean) levels of IL -8 and TNF-alpha were extremely high in sputum (13,780 +/- 916 and 239.3 +/ - 23.5 ng/liter, respectively) but did not change significantly with clinic al deterioration of the patient (P > 0.23), IL-8 and TNF-alpha were general ly undetectable in serum, and therefore these measures were unhelpful. Drop in forced expiratory volume in 1 s was the only clinical or laboratory par ameter that was close to being a determinant of respiratory exacerbation (P = 0.055). This study provides evidence of intense immunological activity o ccurring continually within the lungs of adult CF patients. Measurement of cytokines and inflammatory mediators in CF sputum is not helpful for identi fying acute respiratory exacerbations.