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Acute respiratory failure is a frequent complication of acute pancreatitis and is a common cause of morbidity and mortality (1). Pulmonary changes compatible with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are frequent in patients with fatal acute pancreatitis (2, 3). Despite the prevalence of this pulmonary complication, pancreatitis-associated lung injury is a complex and incompletely understood disease. The underlying mechanisms associated with the development of acute lung injury in pancreatitis are myriad and include the full orchestra of the inflammatory response, including neutrophils, cytokines, chemokines, specific receptors, and adhesion molecules.Circulating neutrophils have long been implicated as important mediators of ALI and ARDS. Animal studies that used different models of experimental pancreatitis (noninvasive model that used choline-deficient ethionine-supplemented diet, biliopancreatic duct injection of bile acid, intravenous infusion of the synthetic cholecystokinin analog cerulein) all have suggested that neutrophil activation plays an important role in mediating lung injury (4, 5). Additional studies have documented that pretreatment of animals with antineutrophil serum markedly depletes circulating neutrophils, reduces the severity of pancreatitis, and prevents lung injury (6). Other studies have identified that trypsin and activation of circulating trypsinogen contribute to pancreatitis-associated lung injury and that pulmonary injury induced by protease infusions was dose-dependent and was ameliorated by neutrophil depletion (7).Further recent studies support the important role that neutrophils play in pancreatitis-associated ALI. CxC chemokines are potent neutrophil chemoattractants and activators and include cytokine-induced neutrophil chemoattractant. Bhatia et al. (8) confirmed that treatment with anti-cytokine-induced neutrophil chemoattractant antibody afforded significant protection against pancreatitis-associated lung injury in a rat cerulein pancreatitis model. CD40, a member of the tumor necrosis factor receptor family, is expressed on a variety of hematopoietic cells and is crucial in orchestrating both humoral and cellular immune responses. Frossard et al. (9) recently documented that CD40 ligand-deficient mice were protected against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.A recent prospective clinical study (10) documented the systemic inflammatory response in a small cohort of patients (n = 11) with acute pancreatitis. This study determined that pancreatitis patients who developed ALI had significantly higher serum concentrations of interleukin-8 and interleukin-6 and neutrophil CD11b expression (indicative of neutrophil activation) compared with pancreatitis patients who did not develop ALI.Severity of pancreatitis-associated lung injury in the experimental setting commonly has been quantified by measurement of pulmonary microvascular permeability, lung edema, and lung myeloperoxidase content as a measure of neutrophil sequestration. These methods have not truly assessed the state of neutrophil activation in the target tissue. Furthermore, they are not easily applicable to clinical medicine in the evaluation and treatment of patients with ALI and ARDS.The report by Dr. Hartwig and colleagues (11) in this issue of Critical Care Medicine continues to advance our understanding of the complex pathophysiology of pulmonary injury associated with pancreatitis and the critical role of the neutrophil. Their report has validated a novel technique to measure pulmonary neutrophil activity by using leukocyte uptake of the glucose analog [18F]fluorodeoxyglucose (18FDG). The authors present a series of elegant studies investigating the pulmonary response to pancreatitis early (6 hrs) after induction of mild and severe experimental pancreatitis in a rat model. They documented that 18FDG neutrophil uptake better quantitated the contribution of activated neutrophils to lung tissue injury than other measurements of neutrophil accumulation or sequestration confirmed by measurement of myeloperoxidase activity and chemotactic peptide uptake.