OXYGEN MITIGATES THE INFLAMMATORY RESPONSE IN A MODEL OF HEMORRHAGE AND ZYMOSAN-INDUCED INFLAMMATION. Issue 2 (February 2016)

• Record Type: Journal Article
• Authors: Rahat, Michal A.; Brod, Vera; Amit-Cohen, Bat-Chen; Henig, Oryan; Younis, Said; Bitterman, Haim
• Is Part Of: Shock. Volume 45:Issue 2(2016:Feb.)
• Page Start: 198
• Page End: 208
• Publication Date: 2016-02
• Subjects: Macrophages -- oxygen therapy -- sequential injuries -- single hits; Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000000492
• Languages: English
• ISSNs: 1073-2322

Abstract

Abstract : ABSTRACT: Sequential insults (hits) may change the inflammatory reaction that develops in response to separate single hits (e.g., injury, infection); however, their effects on the long-term clinical outcome are still only partially elucidated. Double-hit models are typically severe and fatal. We characterized in C57BL/6 mice a moderate double-hit model of hemorrhage (35%–40% of total blood volume) and resuscitation, followed by peritoneal injection of zymosan A that induced local and systemic inflammation with 58% mortality. This model allowed exploration of the inflammatory response over time in the surviving mice. We show that after 2 days, mice subjected to the double-hit model had elevated proinflammatory systemic and local peritoneal cytokine response (interleukin [IL]-1β, tumor necrosis factor-α, IL-6) and moderately elevated anti-inflammatory cytokines (IL-10, transforming growth factor-β), compared with the single-hit and sham mice. However, this dynamically changed, and by day 7, proinflammatory cytokines were reduced, and anti-inflammatory cytokines were markedly ( P < 0.05) elevated in the double-hit group. Mice in the double-hit group that inhaled 100% oxygen intermittently for 6 h every day exhibited markedly reduced serum proinflammatory cytokines as early as day 2 ( P < 0.05), inhibited macrophage infiltration into the peritoneum (by 13-fold; P < 0.05), and substantially increased survival rates of 85% ( P = 0.00144). Oxygen mitigates the inflammatory response and exerts a beneficial effect on survival in a double-hit model of hemorrhage and zymosan-induced inflammation.