Low‐dose TNF augments fracture healing in normal and osteoporotic bone by up‐regulating the innate immune response

• DOI: 10.15252/emmm.201404487
• Publication Date: 2015-03-15T00:32:33Z
• Authors: James K Chan; Graeme E Glass; Adel Ersek; Andrew Freidin; Garry A Williams; Kate Gowers; Ana I Espirito Santo; Rosemary Jeffery; William R Otto; Richard Poulsom; Marc Feldmann; Sara M Rankin; Nicole J Horwood; Jagdeep Nanchahal
• Keywords: Medicine (General); Neutrophils; TNF; 610; QH426-470; bone; Bone and Bones; Monocytes; Fractures, Bone; Mice; 03 medical and health sciences; R5-920; Genetics; Animals; Humans; Research Articles; Chemokine CCL2; Fracture Healing; 0303 health sciences; Tumor Necrosis Factor-alpha; Immunity, Innate; Recombinant Proteins; 3. Good health; Disease Models, Animal; fracture; inflammation; CCL2

Abstract The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating that could be translated to the clinical arena. We previously reported addition low‐dose recombinant human TNF (rh ) at fracture site augmented repair in a murine tibial model. Here, we show local rh treatment is only effective when administered within 24 h injury, neutrophils are major inflammatory cell infiltrate. Systemic administration anti‐ impaired healing. Addition enhanced neutrophil recruitment and promoted monocytes through CCL 2 production. Conversely, depletion or inhibition chemokine receptor CCR resulted significantly Fragility, osteoporotic, fractures represent medical problem as they associated with permanent disability premature death. Using model fragility fractures, found improved during early phase repair. If clinically, this promotion would reduce morbidity mortality delayed patient mobilization.