Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury

Complement factor C5a acting via C5a receptors (C5aR) is recognized as an a naphylotoxin and chemoattractant that exerts proinflammatory effects in man y pathological states. The effects of C5a and C5aR in acute pancreatitis an d in pancreatitis-associated lung injury were evaluated using genetically a ltered mice that either lack C5aR or do not express C5. Pancreatitis was in duced by administration of 12 hourly injections of cerulein (50 mug/kg ip). The severity of pancreatitis was determined by measuring serum amylase, ne utrophil sequestration in the pancreas, and acinar cell necrosis. The sever ity of lung injury was evaluated by measuring neutrophil sequestration in t he lung and pulmonary microvascular permeability. In both strains of geneti cally altered mice, the severity of pancreatitis and pancreatitis-associate d lung injury was greater than that noted in the comparison wild-type strai ns of C5aR- and C5-sufficient animals. This exacerbation of injury in the a bsence of C5a function indicates that, in pancreatitis, C5a exerts an anti- inflammatory effect. Potentially, C5a and its receptor are capable of both promoting and reducing the extent of acute inflammation.