Ulinastatin – a newer potential therapeutic option for multiple organ dysfunction syndrome

Despite significant improvements in medical and surgical management, multiple organ dysfunction syndrome (MODS) or multiple organ failure following conditions such as acute pancreatitis, severe sepsis, and traumatic, hemorrhagic, and endotoxin shocks is still accompanied with a high mortality rate. In light of the crucial role of immunologic derangement recently conceptualized in these conditions, ulinastatin, a urinary trypsin inhibitor, is considered as a potentially beneficial immunomodulator drug for MODS. Mechanisms involving protections against tissue organs and endothelial cell and anti-inflammatory effects by ulinastatin are dependent on the inhibition of polymorphonuclear leukocyte (PMN)-derived elastase, tumor necrosis factor α, and other pro-inflammatory cytokines and interleukins (IL-1, IL-6, and IL-8). Ulinastatin also suppresses the activation of PMN cells, macrophages, and platelets. Derived from these properties, ulinastatin has been investigated as a potential clinical therapy for indications including shock and pancreatitis and approved in Japan and China with ongoing clinical trials around the globe. Off-label potential uses of ulinastatin have been reported in preterm labor and hematological, hepatic, renal, and cardiovascular diseases including vasculitis syndromes such as Kawasaki disease.