Abstract 1943 Poster Session II, Sunday, 5/2 (poster 191)

Ischemia reperfusion injury (IRI) is the most common cause of acute renal failure, and patients with IRI to the kidney often develop lung dysfunction. We have previously reported that neutrophils accumulate in the lungs of mice following bilateral renal IRI, which is associated with the induction of leukocyte adhesion molecules in lung. However, lung neutrophils accumulate 4 h after renal IRI, while adhesion molecules are upregulated by 8 h after IRI, suggesting that the early phases of lung inflammation are adhesion molecule independent. The purpose of the present study was to test the hypothesis that inflammatory cytokine concentrations are upregulated prior to adhesion molecule upregulation and concomitant with neutrophil accumulation. We measured plasma concentrations for TNFα, IL-1β, and IL-6 in male C57/BL6 mice subjected to 45 min bilateral renal ischemia followed by reperfusion from 30 min to 72 h. TNFα levels were 4.0 ± 6.2 pg/ml in control mice, and undetectable in surgical control animals. A significant increase in TNFα concentration was detected by 4h of renal reperfusion, with peak values of 514.3 ± 123.5 pg/ml by 24 h. A more rapid increase in IL-1β concentration was detected, reaching a peak of 396.9 ± 205 pg/ml by 4 h, and declined to 49.4 ± 36.2 by 6 h. Similarly, IL-6 concentrations reached peak values by 4 h, subsequently declining toward baseline values by 12 h. We conclude that 1) plasma pro-inflammatory cytokines may play an important role in lung inflammation following renal IRI, by a direct effect on neutrophil function and by inducing adhesion molecules in the lung and 2) the cytokine inductions may play a role in adhesion molecule-independent lung inflammatory responses.