Treatment with neutralising antibody against cytokine induced neutrophil chemoattractant (CINC) protects rats against acute pancreatitis associated lung injury

Background-Lung injury manifest clinically as adult respiratory distress sy ndrome (ARDS) is a common cause of morbidity and mortality following acute pancreatitis (AP). Neutrophils play a critical role in the progression of A P to ARDS. C-x-C chemokines are potent neutrophil chemoattractants and acti vators and have been implicated in AP. Aims-To evaluate the effect of blocking the C-x-C chemokine, cytokine induc ed neutrophil chemoattractant (CINC), in AP on pancreatic inflammation and the associated lung injury in rats. Methods-AP was induced by hourly intraperitoneal injections of caerulein. G oat anti-CINC antibody was administered either before or after starting cae rulein injections to evaluate the prophylactic and therapeutic effects, res pectively. Severity of AP was determined by measuring plasma amylase, pancr eatic water content, and pancreatic myeloperoxidase (MPO) activity as a mea sure of neutrophil sequestration in the pancreas. Lung injury was determine d by measurement of pulmonary microvascular permeability and lung MPO activ ity. Results-Treatment with anti-CINC antibody had little effect on caerulein in duced pancreatic damage. However, it reduced the caerulein mediated increas e in lung MPO activity as well as lung microvascular permeability when admi nistered either prophylactically (lung MPO (fold increase over control): 1. 53 (0.21) v 3.30 (0.46), p<0.05; microvascular permeability (L/P%): 0.42 (0 .07) v 0.77 (0.11), p<0.05) or therapeutically (lung MPO (fold increase ove r control): 2.13 (0.10) v 4.42 (0.65), p<0.05; microvascular permeability ( L/P%): 0.31 (0.05) v 0.79 (0.13), p<0.05). Conclusion-Treatment with anti-CINC antibody afforded significant protectio n against pancreatitis associated lung injury. These results suggest that C INC plays an important role in the systemic inflammatory response in AP.