Treatment with Met-RANTES reduces lung injury in caerulein-induced pancreatitis

Background: Severe acute pancreatitis leads to a systemic inflammatory response characterized by widespread leucocyte activation and, as a consequence, distant lung injury. In CC chemokines the first two cysteine residues are adjacent to each other. The aim of this study was to evaluate the effect of Met‐RANTES, a CC chemokine receptor antagonist, on pancreatic inflammation and lung injury in caerulein‐induced acute pancreatitis in mice. Methods: Acute pancreatitis was induced in mice by hourly intraperitoneal injection of caerulein. Met‐RANTES was administered either 30 min before or 1 h after starting caerulein injections, and pancreatic inflammation and lung injury were assessed. There were five groups of eight mice each including controls. Results: Treatment with Met‐RANTES had little effect on caerulein‐induced pancreatic damage. Met‐RANTES, however, reduced lung injury when given either before administration of caerulein (mean(s.e.m.) lung myeloperoxidase (MPO) 1·47(0·19) versus 3·70(0·86)‐fold increase over control, P = 0·024; mean(s.e.m.) microvascular permeability 1·15(0·05) versus 3·57(0·63) lavage to plasma fluorescein isothiocyanate‐labelled albumin fluorescence ratio (L/P) per cent, P = 0·002) or after caerulein administration (lung MPO 1·96(0·27) versus 3·65(0·63)‐fold increase over control, P = 0·029; microvascular permeability 0·94(0·04) versus 2·85(0·34) L/P per cent, P < 0·001). Conclusion: Treatment with Met‐RANTES reduces lung damage associated with caerulein‐induced pancreatitis in mice. Chemokine receptor antagonists may be of use for the treatment of the systemic complications of acute pancreatitis. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Chemokine blockade may have clinical potential