Taurine prevents interleukin-2-induced acute lung injury in rats.
BACKGROUND
The therapeutic efficacy of interleukin-2 (IL-2) has been limited by a dose-dependent vascular leak syndrome. This may be related to neutrophil-mediated endothelial injury. Taurine has been shown to decrease this injury in vitro. This study investigates the role of taurine in preventing IL-2-induced lung injury, and the role of neutrophil-endothelial interactions in mediating this injury.


METHODS
Study 1: Sprague-Dawley rats (n = 12/groups) were randomised to controls, IL-2-treated (1 x 10(6) units), and IL-2-treated with taurine (4% solution, orally for 48 h prior to IL-2 therapy). Lung injury was measured by extravascular lung water (wet/dry weight) and bronchoalveolar lavage protein concentration. Neutrophil infiltration was evaluated by measuring myeloperoxidase activity and bronchoalveolar lavage neutrophil concentration. Study 2: Rats (n = 10/group) were randomised into the same groups as study 1. Neutrophil-endothelial interactions in mesenteric vessels were assessed by intravital microscopy at half-hourly intervals.


RESULTS
Taurine reduced IL-2-induced acute lung injury as reflected by a decrease in wet-to-dry lung weight ratio from 7.2 +/- 0.5 in the IL-2 group to 4.7 +/- 0.3 in the taurine group (p < 0.05), and a decrease in bronchoalveolar neutrophil concentration from 823 +/- 19.5 in the IL-2 group to 538 +/- 18 in the taurine group (p < 0.05). Intravital microscopy demonstrated that IL-2 increased leucocyte adhesion and migration in mesenteric vessels, and that this was significantly reduced by taurine.


CONCLUSIONS
These data suggest that taurine prevents IL-2-induced tissue injury in part by decreasing neutrophil-endothelial interactions.
Abdih
H
H
Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
Kelly
C J
CJ
Bouchier-Hayes
D
D
Barry
M
M
Kearns
S
S
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D013654:Taurine / Q000494:pharmacology*
D007376:Interleukin-2; D011506:Proteins; D013654:Taurine; D009195:Peroxidase