Selective Inhibition of IL-6 Trans-Signaling Has No Beneficial Effect on the Posttraumatic Cytokine Release after Multiple Trauma in Mice

Abstract

While improvements in pre-hospital and in-hospital care allow more multiple trauma patients to advance to intensive care, the incidence of posttraumatic multiple organ dysfunction syndrome (MODS) is on the rise. Herein, the influence of a selective IL-6 trans-signaling inhibition on posttraumatic cytokine levels was investigated as an approach to prevent MODS caused by a dysbalanced posttraumatic immune reaction. Therefore, the artificial IL-6 trans-signaling inhibitor sgp130Fc was deployed in a murine multiple trauma model (femoral fracture plus bilateral chest trauma). The traumatized mice were treated with sgp130Fc (FP) and compared to untreated mice (WT) and IL-6 receptor knockout mice (RKO), which received the same traumas. The overall trauma mortality was 4.4%. Microscopic pulmonary changes were apparent after multiple trauma and after isolated bilateral chest trauma. Elevated IL-6, MCP-3 and RANTES plasma levels were measured after trauma, indicating a successful induction of a systemic inflammatory reaction. Significantly reduced IL-6 and RANTES plasma levels were visible in RKO compared to WT. Only a little effect was visible in FP compared to WT. Comparable cytokine levels in WT and FP indicate neither a protective nor an adverse effect of sgp130Fc on the cytokine release after femoral fracture and bilateral chest trauma.

Keywords

• multiple trauma
• MODS
• sgp130Fc
• trans-signaling
• inflammatory cytokines