Decreased leukocyte recruitment in the mesenteric microcirculation of rats with cirrhosis is partially restored by treatment with peginterferon: An in vivo study

Background/Aims Patients with liver cirrhosis are predisposed to develop bacterial infections. An essential process in inflammatory responses is the recruitment of circulating leukocytes through the activation of adhesion molecules. Interferon-alpha2a is a cytokine reported to influence the expression of adhesion molecules. We investigated the effect of peginterferon-alpha2a (PegIFN-α2a) in vivo on the leukocyte recruitment in the mesenteric microcirculation of cirrhotic rats after lipopolysaccharide exposure. Methods Leukocyte rolling, adhesion and extravasation were visualized by intravital microscopy in sham-operated and common bile duct ligated (CBDL) rats. PegIFN-α2a was administered to influence leukocyte recruitment. Endothelial P-selectin, E-selectin and ICAM-1 expression were studied by immunohistochemistry. Results CBDL placebo rats showed significantly impaired rolling, adhesion and extravasation of leukocytes compared to Sham-operated placebo rats. Endothelial P-selectin, E-selectin and ICAM-1 expressions in CBDL placebo rats were significantly reduced compared to Sham-operated placebo rats. PegIFN-α2a 18 μg normalized number of rolling leukocytes in CBDL rats, without influencing on adhering and extravasated leukocytes. PegIFN-α2a upregulates the expression of P-selectin and E-selectin in CBDL rats, but ICAM-1 expression remained significantly lower than in Sham rats. Conclusions Leukocyte recruitment is significantly impaired in the mesenteric microcirculation of cirrhotic rats. This deficiency appears to result from a reduced endothelial P-selectin, E-selectin and ICAM-1 expression. Peginterferon-α2a treatment normalizes rolling of leukocytes in cirrhotic rats by upregulation of P-selectin and E-selectin expressions, but has no influence on adhesion and extravasation possibly due to the absence of effect on ICAM-1 expression.