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The sialyl Lewis X analogue, CY-1503, down-regulates leucocyte-endothelium interactions and the inflammatory response
F J García-Criado1, J J Valdunciel-García, J García-García
1Department of Surgery, Faculty of Medicine, University of Salamanca, Spain.
Objective:
To elucidate mechanisms of protection of ischaemic liver with the sialyl Lewis X analogue CY-1503 by regulation of inflammatory mediators such as oxygen free radicals and cytokines as well as blocking the migration of leucocytes.
Design:
Laboratory study.
Setting:
Teaching hospital, Spain.
Animals:
122 male Sprague-Dawley rats divided into four groups: normal (n = 18), sham-operated (n = 28), ischaemic controls (n = 38), and CY-1503 (n = 38).
Interventions:
Warm total hepatic ischaemia for 90 minutes followed by various periods of reperfusion.
Main Outcome Measures:
Survival, liver histology, liver function, neutrophil infiltration, and free radical and cytokine concentrations.
Results:
2/20 ischaemic controls survived, compared with 14/20 given CY-1503. Liver function was better, as was histological appearance judged by the Suzuki score); myeloperoxidase activity was significantly decreased (n = 6 in each group, p<0.01) as were concentrations of free radicals (n = 12 in each group, p<0.05) in the group given CY-1503. CY-1503 had no effect on concentrations of the cytokines tumour necrosis factor-alpha or interleukin 1-alpha.
Conclusions:
CY-1503 exerts a protective effect in that it able to down-regulate concentrations of free radicals in our rat model. It is a potent inhibitor of neutrophil migration, but has no effect on cytokine concentrations.