Background: The therapeutic efficacy of interleukin-2 (IL-2) has been limit
ed by a dose-dependent vascular leak syndrome. This may be related to neutr
ophil-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 interactio
ns in mediating this injury.
Methods: Study 1: Sprague-Dawley rats (n = 12/ groups) were randomised to c
ontrols, 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 pro
tein concentration. Neutrophil infiltration was evaluated by measuring myel
operoxidase activity and bronchoalveolar lavage neutrophil concentration. S
tudy 2: Rats (n = 10/group) were randomised into the same groups as study 1
. Neutrophilendothelial 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 d
ecrease 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 bronchoal
veolar 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.
Conclusion: These data suggest that taurine prevents IL-2-induced tissue in
jury in part by decreasing neutrophil-endothelial interactions. Copyright (
C) 2001 S.Karger AG, Basel.