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).


CONCLUSIONS
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.
Bhatia
M
M
Department of Pharmacology, National University of Singapore, Singapore. mbhatia@nus.edu.sg
Proudfoot
A E I
AE
Wells
T N C
TN
Christmas
S
S
Neoptolemos
J P
JP
Slavin
J
J
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002108:Ceruletide / Q000633:toxicity; D018946:Chemokine CCL5 / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D004353:Drug Evaluation, Preclinical; D008171:Lung Diseases / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008833:Microcirculation; D010195:Pancreatitis / Q000150:complications* / Q000473:pathology; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors; D018746:Systemic Inflammatory Response Syndrome / Q000517:prevention & control*
D000893:Anti-Inflammatory Agents; D018946:Chemokine CCL5; C108335:RANTES, Met-; D019707:Receptors, Chemokine; D002108:Ceruletide