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To assess the cytokine expression (tumor necrosis factor-α [TNF-α], interleukin [IL]-1β, and IL-6) in severe pneumonia, both locally (in the lungs) and systemically (in blood).Prospective sequential study with bronchoalveolar lavage (BAL) and blood sampling.Six-bed respiratory intensive care unit of a 1,000-bed teaching hospital.Thirty mechanically ventilated patients (>48 hrs) were allocated to either the pneumonia group (n = 20) or a control group (n = 10).Protected specimen brush and BAL samples for quantitative cultures, and serum and BAL fluid TNF-α, IL-1β, and IL-6 levels were measured on days 1, 3, and 7. In the control group, the procedure was done on day 1 only.Serum TNF-α levels were significantly higher in patients with pneumonia compared with controls (35 ± 4 vs. 17 ± 3 pg/mL, respectively, p = .001). IL-6 levels in serum and BAL fluid were higher in pneumonia than in control patients (serum, 837 ± 260 vs. 94 ± 35 pg/mL, respectively, p = .017; BAL fluid, 1176 ± 468 vs. 234 ± 83 pg/mL, respectively, p = .05). On days 1, 3, and 7 in patients with pneumonia, IL-1β levels turned out to be higher in BAL fluid than in serum (71 ± 17 vs. 2 ± 1 pg/mL on day 1; 49 ± 8 vs. 6 ± 2 pg/mL on day 3; and 47 ± 16 vs. 3 ± 2 pg/mL on day 7 for BAL fluid and serum, respectively, p < .05). No significant correlation between BAL fluid cytokine levels and lung bacterial burden was shown in presence of antibiotic treatment. Although no clear relationship was found between BAL fluid and serum cytokines and mortality, there was a trend toward higher serum IL-6 levels in nonsurvivors (1209 ± 433 pg/mL) with pneumonia compared with survivors (464 ± 260 pg/mL). In addition, serum TNF-α and IL-6 correlated with multiple organ failure score (r2 = .36, p = .004 for both) and with lung injury score (r2 = .30, p = .01, and r2 = .22, p = .03, for TNF-α and IL-6, respectively).The present study describes the lung and systemic inflammatory response in severe pneumonia. The lung cytokine expression seems to be independent from the lung bacterial burden in the presence of antibiotic treatment. Because of the limited sample size, we did not find a clear relationship between serum and BAL fluid cytokine levels and outcome.