Inflammatory mediators are potential biomarkers for extracorporeal shockwave therapy in horses.

BACKGROUND Extracorporeal shockwave therapy (ESWT) can potentially mask painful injuries in equine athletes. Tests to detect whether a horse has received ESWT prior to competition are needed. Extracorporeal shockwave therapy is known to affect inflammatory mediators in other species, and if these mediators are altered in the horse, these could serve as biomarkers of ESWT. OBJECTIVES To test the hypothesis that a single application of ESWT will alter the circulating protein concentrations of 10 inflammatory mediators in horse plasma. Study design Prospective repeated measures experimental study. METHODS Eleven healthy horses were administered a single dose of ESWT on the dorsal surface of proximal MCIII. Blood samples were collected at -168, -144, -120, -96, -72, -70, -68, -66, -48, -24, -6, -4, -2, 0 h before and 2, 4, 6, 24, 48, 72, 96, 168, 336 and 504 h after ESWT. Plasma concentrations of interleukin 1 beta (IL-1β), IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-15, interferon gamma (IFN-γ), soluble toll-like receptor 2 (sTLR2) and tumour necrosis factor alpha (TNF-α) were measured to assess the effects of ESWT on these mediators. RESULTS Baseline concentrations of inflammatory mediators did not change substantially during the week prior to ESWT. Plasma concentrations of 5 inflammatory factors changed following ESWT. IL-1β and IL-6 were significantly down-regulated (p<0.01), while TNF-α, IL-1RA and TLR2 were significantly up-regulated (p<0.01). The remaining cytokines were not significantly affected by ESWT. Main limitations This study was performed in a small number of sedentary, healthy pasture-kept horses using a single dose of ESWT applied to a single location. Additional studies are necessary to determine the effect of ESWT on inflammatory mediators in athletic horses undergoing treatment for musculoskeletal injuries. CONCLUSIONS Plasma concentrations of TNF-α, IL-1β, IL-1RA, IL-6 and TLR2 were significantly affected by ESWT, and deserve further investigation as possible biomarkers of ESWT.

[1]  Jiang Chen,et al.  Effects of Shock Waves on Expression of IL-6, IL-8, MCP-1, and TNF-α Expression by Human Periodontal Ligament Fibroblasts: An In Vitro Study , 2016, Medical science monitor : international medical journal of experimental and clinical research.

[2]  M. Robinson,et al.  Plasma interleukin-6 concentration in Standardbred racehorses determined by means of a novel validated ELISA. , 2015, American journal of veterinary research.

[3]  C. García,et al.  Evaluación del daño tisular producido por la nefrolitotomía percutánea mediante la determinación sérica de mediadores inflamatorios , 2015 .

[4]  F. Gudé,et al.  Assessment of tissue damage due to percutaneous nephrolithotomy using serum concentrations of inflammatory mediators. , 2015, Actas urologicas espanolas.

[5]  H. Langberg,et al.  In vivo biological response to extracorporeal shockwave therapy in human tendinopathy. , 2015, European cells & materials.

[6]  J. Grieger,et al.  scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy , 2015, Gene Therapy.

[7]  T. Shindo,et al.  Extracorporeal low-energy shock-wave therapy exerts anti-inflammatory effects in a rat model of acute myocardial infarction. , 2014, Circulation journal : official journal of the Japanese Circulation Society.

[8]  E. Galliera,et al.  Soft-focused extracorporeal shock waves increase the expression of tendon-specific markers and the release of anti-inflammatory cytokines in an adherent culture model of primary human tendon cells. , 2014, Ultrasound in medicine & biology.

[9]  K. Sarıca,et al.  Evaluating ESWL-induced renal injury based on urinary TNF-α, IL-1α, and IL-6 levels , 2012, Urological Research.

[10]  A. Evan,et al.  Effect of shock wave number on renal oxidative stress and inflammation , 2011, BJU international.

[11]  J. Lavoie,et al.  Optimization of a procedure to accurately detect equine TNFα in serum samples. , 2010, Veterinary immunology and immunopathology.

[12]  H. Erb,et al.  Serum interleukin-6 (IL-6) and IL-10 concentrations in normal and septic neonatal foals. , 2009, Veterinary immunology and immunopathology.

[13]  K. Ren,et al.  Role of interleukin-1β during pain and inflammation , 2009, Brain Research Reviews.

[14]  D. Strong,et al.  In vitro and in vivo modulation of the equine immune response by parapoxvirus ovis. , 2008, Equine veterinary journal.

[15]  Jui-Sheng Sun,et al.  Effects of shock waves on tenocyte proliferation and extracellular matrix metabolism. , 2008, Ultrasound in medicine & biology.

[16]  Ching‐Jen Wang,et al.  Extracorporeal shock wave enhanced extended skin flap tissue survival via increase of topical blood perfusion and associated with suppression of tissue pro-inflammation. , 2007, The Journal of surgical research.

[17]  D. Hurley,et al.  Exercise-induced alterations in pro-inflammatory cytokines and prostaglandin F2alpha in horses. , 2007, Veterinary immunology and immunopathology.

[18]  R. Evans,et al.  Force platform evaluation of lameness severity following extracorporeal shock wave therapy in horses with unilateral forelimb lameness. , 2006, Journal of the American Veterinary Medical Association.

[19]  M. Revenaugh Extracorporeal shock wave therapy for treatment of osteoarthritis in the horse: clinical applications. , 2005, The Veterinary clinics of North America. Equine practice.

[20]  M. Sitkovsky,et al.  Model organisms: Animal Models of sepsis: setting the stage , 2005, Nature Reviews Drug Discovery.

[21]  S. McClure,et al.  Extracorporeal shock wave therapy: Clinical applications and regulation , 2003 .

[22]  M. Thiel,et al.  Application of shock waves in medicine. , 2001, Clinical orthopaedics and related research.

[23]  J. Ogden,et al.  Principles of shock wave therapy. , 2001, Clinical orthopaedics and related research.

[24]  C. Dinarello Impact of Basic Research On Tomorrow's MedicineProinflammatory Cytokines , 2000 .

[25]  A. Hasegawa,et al.  Molecular cloning and functional expression of equine interleukin-1 receptor antagonist. , 1997, Veterinary immunology and immunopathology.

[26]  J. Rompe,et al.  Analgesic effect of extracorporeal shock-wave therapy on chronic tennis elbow. , 1996, The Journal of bone and joint surgery. British volume.

[27]  A. Hasegawa,et al.  Molecular cloning of equine interleukin-1α and -β cDNAs , 1995 .

[28]  D. Horohov,et al.  Molecular cloning and sequencing of equine interleukin 4. , 1994, Veterinary immunology and immunopathology.

[29]  D. Horohov,et al.  Molecular cloning and expression of equine interleukin 2. , 1993, Veterinary immunology and immunopathology.

[30]  W. Chou,et al.  Extracorporeal shockwave therapy for treatment of keloid scars , 2018, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[31]  G. Ueltschi,et al.  Short term analgesic effect of extracorporeal shock wave therapy in horses with proximal palmar metacarpal/plantar metatarsal pain. , 2009, Veterinary journal.

[32]  D. Antczak,et al.  Cloning and sequencing of horse interferon-gamma cDNA , 2004, Immunogenetics.