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

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Abstract
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.
Funding Information
  • Wellcome Trust; National Medical Research Council; Academic Research Fund