LOCAL PSEUDOMONAS INSTILLATION INDUCES CONTRALATERAL LUNG INJURY AND PLASMA CYTOKINES

We investigated whether local bacterial instillation leads to lung inj ury in noninstilled lung regions and examined local and systemic cytok ine accumulation. Rats were challenged by intrabroncheal instillation of Pseudomonas aeruginosa, 10(7) colony-forming units (CFU) (HD group, n = 11), 4 x 10(6) CFU (LD group, n = 10), or saline (control group, n = 12). Tc-99m-labeled macroaggregated albumin was added to the P. ae ruginosa or saline solution for later documentation of the instilled a rea. At 4 h the right lung, including instilled segment, and the left lung were sampled. Lung injury was assessed by lung tissue to plasma I -125-labeled albumin (T/P) and lung wet-dry (W/D) ratios. We measured plasma and bronchoalveolar lavage fluid (BALF) levels of tumor necrosi s factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC). HD bacterial instillation induced neutrophil recruitment and TNF and CINC elevation in BALF (p < 0.05) associated with increased T/P (p < 0 .005) and W/D (p < 0.05) ratios in both instilled and the noninstilled lungs as compared with the saline-instilled and noninstilled controls . LD bacterial instillation induced neutrophil recruitment and TNF and CINC elevation only in the instilled lung (p < 0.05), and not in the noninstilled lung, and did not increase the T/P or W/D ratio. Plasma l evels of TNF and CINC were increased in the HD, but not the LD, group when compared with the saline controls (p < 0.05). These data indicate that, when the dose is high enough to cause an excess inflammatory re sponse, local bacterial instillation leads to neutrophil sequestration , lung injury, and cytokine elevation in the noninstilled lung associa ted with systemic cytokine release.