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Effects of intra-articularly administered endotoxin on clinical signs of disease and synovial fluid tumor necrosis factor, interleukin 6, and prostaglandin E2 values in horses.

Abstract: In each of 4 horses, sterile synovitis was induced by intra-articular injection of 3 micrograms of Escherichia coli endotoxin (lipopolysaccharide, LPS) into one antebrachiocarpal joint; an equal volume (2 ml) of phosphate-buffered saline solution (PBSS) was injected into the opposite, control carpus. Blood and 1.5 ml of synovial fluid were obtained at postinjection hours (PIH) 0, 2, 4, 8, 12, 18, 42, 66, and 144. Synovial fluid sample collection was accomplished by use of an indwelling, intra-articular catheter through PIH 12, and by arthrocentesis subsequently. Joint fluid samples were analyzed for cell counts, protein concentration, cytologic variables, and tumor necrosis factor (TNF), interleukin 6 (IL-6), and prostaglandin E2 (PGE2) values. Tumor necrosis factor and IL-6 activities and WBC count were also measured in blood. To monitor local inflammation, skin temperature of each carpus was imaged, using a thermographic scanner prior to each sample collection time. Horses had minimal systemic effects. Mean (+/- SEM) rectal temperature increased significantly to 39.02 +/- 0.15 C only at PIH 18 after intra-articular injection of LPS. One horse had signs of mild depression from PIH 7 to 18, but its vital signs did not change appreciably. Each horse had mild signs of discomfort in the LPS-injected limb from PIH 1 to 3 until PIH 8 to 10. Mean peak surface temperature of the LPS-injected carpi was significantly higher than that of control carpi from PIH 8 to 144 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1993-03-01 PubMed ID: 8498739
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research analyzes the impact of endotoxins introduced within the joint, on the clinical symptoms and various inflammatory factors in horses. It also studies the body’s systemic response to inflammation.

Experimental Procedure

The experiment was carried out on four horses in which sterile synovitis, a type of joint inflammation, was induced. This was achieved by injecting a lethal toxins, called lipopolysaccharide (LPS), into one joint of the horse. This procedure was designed to study the effects of an immune response triggered by bacterial infection locally within the joint.

  • The toxin chosen was derived from a strain of bacteria called Escherichia coli, and the amount administered to each horse was 3 micrograms.
  • The opposite joint was used as a control, and an equal volume of a saline solution was administered instead of the toxin.
  • The joint fluid and blood samples were collected at different time intervals from 0 to 144 postinjection hours (PIH).
  • For the initial 12 hours of the experiment, samples were collected via an indwelling catheter inserted inside the joint. After that, samples were obtained through a procedure called arthrocentesis (a minimally invasive procedure to collect fluids from the joint).

Analytical Procedure

The collected joint fluid was then analyzed for a variety of factors.

  • Components such as cell counts, protein concentration, and cytologic variables were determined.
  • The fluid was examined for the presence of certain chemicals associated with inflammation and immune response: tumor necrosis factor (TNF), interleukin 6 (IL-6), and prostaglandin E2 (PGE2).
  • Blood samples were also analyzed for TNF and IL-6 activities and white blood cell count.
  • Additionally, the skin temperature at the joint site was captured using a thermographic scanner before each sample collection, as a measure to monitor local inflammation.

Findings

The horses showed minimal systemic, or full-body, reactions to the induced inflammation in the joint. There was only a slight increase in rectal temperature and one horse showed signs of mild depression, but nothing significantly harmful. However, there were localized symptoms seen in the leg that received the toxin injection, including mild discomfort for a limited duration. The surface temperature of the treated joint also showed a significant increase, indicating inflammation at the injection site.

Cite This Article

APA
Hawkins DL, MacKay RJ, Gum GG, Colahan PT, Meyer JC. (1993). Effects of intra-articularly administered endotoxin on clinical signs of disease and synovial fluid tumor necrosis factor, interleukin 6, and prostaglandin E2 values in horses. Am J Vet Res, 54(3), 379-386.

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 54
Issue: 3
Pages: 379-386

Researcher Affiliations

Hawkins, D L
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610.
MacKay, R J
    Gum, G G
      Colahan, P T
        Meyer, J C

          MeSH Terms

          • Analysis of Variance
          • Animals
          • Body Temperature / drug effects
          • Dinoprostone / metabolism
          • Endotoxins / administration & dosage
          • Endotoxins / toxicity
          • Escherichia coli
          • Horses
          • Injections, Intra-Articular
          • Interleukin-6 / metabolism
          • Leukocyte Count / drug effects
          • Lipopolysaccharides / administration & dosage
          • Lipopolysaccharides / toxicity
          • Male
          • Orchiectomy
          • Synovial Fluid / drug effects
          • Synovial Fluid / metabolism
          • Synovitis / etiology
          • Synovitis / physiopathology
          • Time Factors
          • Tumor Necrosis Factor-alpha / metabolism

          Citations

          This article has been cited 11 times.
          1. Martinez RE, Leatherwood JL, Arnold CE, Glass KG, Walter KW, Valigura HC, Norton SA, White-Springer SH. Responses to an intra-articular lipopolysaccharide challenge following dietary supplementation of Saccharomyces cerevisiae fermentation product in young horses. J Anim Sci 2021 Oct 1;99(10).
            doi: 10.1093/jas/skab272pubmed: 34619765google scholar: lookup
          2. Watkins A, Fasanello D, Stefanovski D, Schurer S, Caracappa K, D'Agostino A, Costello E, Freer H, Rollins A, Read C, Su J, Colville M, Paszek M, Wagner B, Reesink H. Investigation of synovial fluid lubricants and inflammatory cytokines in the horse: a comparison of recombinant equine interleukin 1 beta-induced synovitis and joint lavage models. BMC Vet Res 2021 May 12;17(1):189.
            doi: 10.1186/s12917-021-02873-2pubmed: 33980227google scholar: lookup
          3. Bittar IP, Neves CA, Araújo CT, Oliveira YVR, Silva SL, Borges NC, Franco LG. Dose-Finding in the Development of an LPS-Induced Model of Synovitis in Sheep. Comp Med 2021 Apr 1;71(2):141-147.
            doi: 10.30802/AALAS-CM-20-000032pubmed: 33568256google scholar: lookup
          4. Mendez ME, Sebastian A, Murugesh DK, Hum NR, McCool JL, Hsia AW, Christiansen BA, Loots GG. LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice. J Bone Miner Res 2020 Nov;35(11):2229-2241.
            doi: 10.1002/jbmr.4117pubmed: 32564401google scholar: lookup
          5. Sotelo EDP, Vendruscolo CP, Fülber J, Seidel SRT, Jaramillo FM, Agreste FR, Silva LCLCD, Baccarin RYA. Effects of Joint Lavage with Dimethylsulfoxide on LPS-Induced Synovitis in Horses-Clinical and Laboratorial Aspects. Vet Sci 2020 Apr 30;7(2).
            doi: 10.3390/vetsci7020057pubmed: 32365982google scholar: lookup
          6. Hunt CL, Leatherwood JL, Coverdale JA, Sigler DL, Vogelsang MM, Arnold CE. Effects of repeated arthrocentesis on systemic cytokine expression and leukocyte population in young horses challenged with intra-articular lipopolysaccharide. J Anim Sci 2019 Jan 1;97(1):184-191.
            doi: 10.1093/jas/sky423pubmed: 30423145google scholar: lookup
          7. Moreira JJ, Moraes AP, Brossi PM, Machado TS, Michelacci YM, Massoco CO, Baccarin RY. Autologous processed plasma: cytokine profile and effects upon injection into healthy equine joints. J Vet Sci 2015;16(1):47-55.
            doi: 10.4142/jvs.2015.16.1.47pubmed: 25269714google scholar: lookup
          8. Freitas GC, Carregaro AB, Gehrcke MI, De La Côrte FD, Lara VM, Pozzobon R, Brass KE. Epidural analgesia with morphine or buprenorphine in ponies with lipopolysaccharide (LPS)-induced carpal synovitis. Can J Vet Res 2011 Apr;75(2):141-6.
            pubmed: 21731186
          9. de Grauw JC, van de Lest CH, van Weeren PR. Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study. Arthritis Res Ther 2009;11(2):R35.
            doi: 10.1186/ar2640pubmed: 19272138google scholar: lookup
          10. Duggan MJS, Kearney C, Baltrimaite M, Labberté MC, Gibney R, Brama PAJ. Refinement of the Lipopolysaccharide-Induced Synovitis Model in Equine Middle Carpal Joints. Animals (Basel) 2025 Aug 22;15(17).
            doi: 10.3390/ani15172474pubmed: 40941269google scholar: lookup
          11. Dörner C, Lagos N, Oyaneder L, Menarim BC, Ramírez-Toloza G. Synovial Fluid Biomarker Profile After Intra-Articular Administration of Neosaxitoxin in Horses: A Feasibility Study. Animals (Basel) 2025 Aug 21;15(16).
            doi: 10.3390/ani15162453pubmed: 40867781google scholar: lookup