Pharmacological inhibition of IL-6 trans-signaling improves compromised fracture healing after severe trauma

Naunyn-Schmiedeberg's Archives of Pharmacology
Kathrin KaiserAnita Ignatius

Abstract

Patients with multiple injuries frequently suffer bone fractures and are at high risk to develop fracture healing complications. Because of its key role both in systemic posttraumatic inflammation and fracture healing, the pleiotropic cytokine interleukin-6 (IL-6) may be involved in the pathomechanisms of trauma-induced compromised fracture healing. IL-6 signals are transmitted by two different mechanisms: classic signaling via the membrane-bound receptor (mIL-6R) and trans-signaling via its soluble form (sIL-6R). Herein, we investigated whether IL-6 classic and trans-signaling play different roles in bone regeneration after severe injury. Twelve-week-old C57BL/6J mice underwent combined femur osteotomy and thoracic trauma. To study the function of IL-6, either an anti-IL-6 antibody, which inhibits both IL-6 classic and trans-signaling, or a soluble glycoprotein 130 fusion protein (sgp130Fc), which selectively blocks trans-signaling, were injected 30 min and 48 h after surgery. Bone healing was assessed using cytokine analyses, flow cytometry, histology, micro-computed tomography, and biomechanical testing. Selective inhibition of IL-6 trans-signaling significantly improved the fracture healing outcome after combined injury, as...Continue Reading

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Citations

Apr 3, 2019·European Journal of Trauma and Emergency Surgery : Official Publication of the European Trauma Society·Philipp StörmannBorna Relja
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Nov 15, 2021·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Mustafa BecerikliBjörn Behr

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Methods Mentioned

BETA
lavage
Protein Assay
enzyme-linked immunosorbent assay
PCR
light microscopy

Software Mentioned

MMAF
FlowJo
GraphPad Prism
LinReg PCR

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