Claude H. Organ, Jr. Memorial Lecture: Splanchnic hypoperfusion provokes acute lung injury via a 5-lipoxygenase–dependent mechanism

Postinjury multiple organ failure (MOF) is the net result of a dysfunctional immune response to injury characterized by a hyperactive innate system and a suppressed adaptive system. Acute lung injury (ALI) is the first clinical manifestation of organ failure, followed by renal and hepatic dysfunction. Circulatory shock is integral in the early pathogenesis of MOF, and the gut has been invoked as the motor of MOF. Mesenteric lymph is recognized as the mechanistic link between splanchnic ischemia/reperfusion and distant organ dysfunction, but the specific mediators remain to be defined. Current evidence suggests the lipid fraction of postshock mesenteric lymph is central in the etiology of ALI. Specifically, our recent work suggests that intestinal phospholipase A2 generated arachidonic acid and its subsequent 5-lipoxygenase products are essential in the pathogenesis of ALI. Proteins conveyed via postshock mesenteric lymph also may have an important role. Elucidating these mediators and the timing of their participation in pulmonary inflammation is critical in translating our current knowledge to new therapeutic strategies at the bedside.