Acute pancreatitis is a multifaceted disease that is associated with considerable morbidity and mortality. In United States alone, more than 300,000 patients are hospitalized annually with pancreatitis leading to 3200 deaths. Pancreatitis is a contributing factor in an additional 4000 deaths annually. It also inflicts a heavy economic burden, the direct cost in the United States alone is more than $2 billion annually. 1 Conventional wisdom states that pancreatitis begins with the intrapancreatic activation of digestive enzyme zymogens, acinar cell injury, 2 and activation of transcription factors such as NF-κB and AP-1. 3, 4 This is followed by a proinflammatory cascade leading to acinar cell necrosis, systemic inflammatory response syndrome (SIRS), and distant organ dysfunction including lung injury that frequently manifests itself as the acute respiratory distress syndrome (ARDS). 5 The ultimate severity of acute pancreatitis depends on the extent of systemic inflammatory response. A whole repertoire of cytokines and chemokines and their receptors play a crucial role in the recruitment of inflammatory cells from the blood into the affected tissue. One inflammatory mediator that has emerged as a pivotal cytokine of the innate immune system in the past few years is the macrophage migration inhibitory factor (MIF), which is the focus of the study by Sakai et al. 6 in the current issue of GASTROENTEROL-