The sialyl lewis X analogue, CY‐1503, down‐regulates leucocyte‐endothelium interactions and the inflammatory response

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‐α or interleukin 1‐α. 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. Copyright © 1999 Taylor and Francis Ltd.