The effect of sRAGE-Fc fusion protein attenuates inflammation and decreases mortality in a murine cecal ligation and puncture model

Abstract

OBJECTIVE: Inhibition of the receptor for advanced glycation end products (RAGE) may attenuate the systemic inflammatory response and ensuing severe sepsis. We report an investigation into the effect of soluble RAGE (sRAGE)-Fc fusion protein in severe sepsis induced by a cecal ligation and puncture (CLP) procedure.

MATERIALS AND METHODS: The experiment was performed using CLP control mice, mice treated with 0.5 or 1.0 μg sRAGE-Fc fusion protein, and sham surgery mice.

RESULTS: Survival benefits over the CLP control group were evident (P = 0.036) in mice given 1.0 μg sRAGE-Fc fusion protein. In addition, the pulmonary inflammation score in the sRAGE-Fc fusion protein-treated group was significantly lower than that in the CLP control group (P < 0.05). Lung tissue in the sRAGE-Fc fusion protein-treated group revealed a significant decrease in the expression of inflammatory cytokines. Furthermore, levels of interleukin (IL)-1β and tumor necrosis factor-α were significantly lower in sRAGE-Fc fusion protein treated groups (P < 0.001). Moreover, IL-6 levels showed a significant difference between CLP control and sRAGE-Fc fusion protein treated groups (P < 0.01).

CONCLUSIONS: sRAGE-Fc fusion protein has beneficial effects in a standard murine model of polymicrobial, intra-abdominal severe sepsis.