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

Jil-Madeline Homeier,Claudia Neunaber,Tilman Graulich,Christian Macke,Marcel Winkelmann,Borna Relja,Katrin Bundkirchen

doi:10.3390/life11111252

Jil-Madeline Homeier, Claudia Neunaber + Show 5 more

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https://doi.org/10.3390/life11111252

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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.

Highlights

Injuries cause 16% of the global burden of diseases [1]
The aim of the present study was to investigate the effects of a selective inhibition of IL-6 trans-signaling by the use of sgp130Fc on the posttraumatic cytokine levels in a well-established murine multiple trauma model, consisting of a femoral fracture and a blunt bilateral chest trauma
Thirteen animals died during the procedure, which resulted in an overall mortality of 4.4%

Summary

Introduction

Injuries cause 16% of the global burden of diseases [1]. Despite constant improvements in pre-hospital and in-hospital trauma care, the mortality rate in severely injured patients who reach the hospital, even in high-income countries, still accounts for 15% [2]. Trauma ranks first in causes for loss of potential life in Germany [2]. Whilst continuing enhancements in primary trauma care could be achieved by the application of refined treatment algorithms [3], the case fatality rate in patients, developing multiple organ dysfunction syndrome (MODS) in the secondary stage after trauma, remains considerably high [4,5,6,7]. Traumatic tissue damage and hemorrhage liberate endogenous mediators to the bloodstream that are physiologically located intracellularly and are known as

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