Increases in IL-6 and Number of Inflammatory Cells in the Lung Lavage Fluid of Adult Mice Exposed to 95% Oxygen: Potential Effect of Budesonide(16,17 -butylidenedioxy-11,21-dihydroxy-pregna-1,4-diene-3,20-dionn3)† 1961

Pulmonary oxygen toxicity is mainly an inflammatory process, triggered by reactive oxygen species via a number of biochemical pathways. Recent evidence implies that ROS may stimulate NF-kB to promote the synthesis of genes for inflammatory cytokines. At the same time, corticosteroids have been implicated in the prevention of activating this step. However, adverse reactions of systemic corticosteroids cause physicians to hesitate their use, not to mention their doubtful effectiveness. Budesonide is a locally acting corticosteroid with little systemic effect. Inhaled either through nebulizers or metered dose inhalers, it has proved the antiinflammatory, and thus antiasthmatic, effects in patients with asthma. If oxygen-induced injury is mediated by factors involved in a similar pathway as described above, budesonide will have protective effects against inflammatory responses of pulmonary oxygen toxicity. We used 10 adult mice in each of the three groups; AC is the room air control group; OC is the oxygen control group in which mice were exposed to 95% oxygen for 48 h; and TX is the treatment group in which mice were exposed to 95% oxygen for 48 h, and during that period they were given budesonide via a nebulizer 500 μg/dose every 12 h for 4 times. The mice were sacrificed with injection of a lethal dose of ketamine. Tracheotomy was done and an 18G ET tube was inserted. The lungs were lavaged with 80ml/kg(or 80 μl/g) isotonic saline slowly injected through the ET tube. The lung lavage fluid was centrifuged at 8000 rpm for 2 minutes. Supernatant was used for analysis of IL-6, while the precipitate was resuspended in 200 μl of isotonic saline for leukocyte count. The simple mean IL-6 values did not show a significant difference between groups (AC 199.4±192.7 pg/ml; OC 274.5±31.3 pg/ml; and TX 269.8±127.0 pg/ml). But considering their skewed distribution in AC and TX groups, the median values showed a conspicuous difference among 3 groups; that is, the median IL-6 value of AC was 124.8 pg/ml, OC 269.8 pg/ml, and TX 217.4 pg/ml. For the cell counts, AC was 189±56/mm³, OC 424±111/mm³, and TX 266±22/mm³ (p < 0.05). In conclusion, budesonide nebulization appears to have protective effects against inflammatory responses of pulmonary oxygen toxicity in adult mice.