Analyze Diet
Equine veterinary journal2025; 58(2); 380-389; doi: 10.1111/evj.70123

Synovial chemokine and cytokine profiles in horses with and without systemic Borrelia burgdorferi infection.

Abstract: Lyme arthritis, a well-documented subtype of arthritis in humans and dogs, is caused by Borrelia burgdorferi and spread primarily through ticks (Ixodes spp.). While Lyme disease in horses is known to cause a variety of clinical signs, its involvement in the development of equine arthritis is controversial. As climate change enables tick populations to expand, more horses could be exposed to B. burgdorferi; therefore, a greater understanding of how Lyme disease affects joints is critical to preserving soundness. Objective: To determine if systemic, naturally occurring Lyme disease had a discernible effect on joint inflammatory markers in horses presenting with a variety of joint pathologies. Methods: Cross-sectional study. Methods: Synovial fluid samples were collected at the start of routine joint injection or immediately prior to surgery and analysed for chemokine and cytokine levels. Serum samples from each horse were tested for outer surface protein (OSP) markers via Lyme Multiplex. Results: Six of twenty-five enrolled horses (24%) tested positive for at least one Lyme outer surface protein marker (OSP A 0/6; OSP C 2/6; OSP F 6/6; mean age 11.17 ± 6.31 years), and three more horses had an equivocal result (OSP A 0/3; OSP C 1/3; OSP F 3/3; mean age 11.67 ± 2.62 years). While most synovial inflammatory markers showed no statistical difference between systemic, serologic Lyme infection status and presumed arthritic joints (p = 0.1-0.7) or trauma-associated joints (p = 0.4-0.9), we observed a noteworthy negative association between CCL2 synovial fluid levels and systemic Lyme status (p = 0.01). Conclusions: Sample size was a primary limitation. Conclusions: The negative association observed between CCL2 synovial fluid levels and systemic Lyme status was also present in arthritic joints of horses with systemic B. burgdorferi infection. Notably, this contrasts with past reports of increased synovial fluid CCL2 levels associated with Lyme arthritis in other species.
Publication Date: 2025-11-26 PubMed ID: 41297916DOI: 10.1111/evj.70123Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

Cite This Article

APA
Clark KF, Lemcke RA, Gasiorowski JC, Wagner B. (2025). Synovial chemokine and cytokine profiles in horses with and without systemic Borrelia burgdorferi infection. Equine Vet J, 58(2), 380-389. https://doi.org/10.1111/evj.70123

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 58
Issue: 2
Pages: 380-389

Researcher Affiliations

Clark, Kyle F
  • Mid-Atlantic Equine Medical Center, Ringoes, New Jersey, USA.
Lemcke, Rachel A
  • Amwell Data Services LLC, Ringoes, New Jersey, USA.
Gasiorowski, Janik C
  • Mid-Atlantic Equine Medical Center, Ringoes, New Jersey, USA.
Wagner, Bettina
  • Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, New York, USA.

MeSH Terms

  • Animals
  • Horses
  • Lyme Disease / veterinary
  • Lyme Disease / metabolism
  • Lyme Disease / microbiology
  • Lyme Disease / immunology
  • Horse Diseases / microbiology
  • Horse Diseases / metabolism
  • Synovial Fluid / chemistry
  • Borrelia burgdorferi
  • Cross-Sectional Studies
  • Cytokines / metabolism
  • Cytokines / genetics
  • Chemokines / metabolism
  • Chemokines / genetics
  • Female
  • Male

Grant Funding

  • American Association of Rehabilitation Veterinarians

References

This article includes 54 references
  1. Jackson M, Vizard A, Anderson G, Clarke A, Whitton R. Association between the purchase price of Thoroughbred yearlings and their performance during the 2‐ and 3‐year‐old racing seasons. Aust Vet J. 2011;89(10):388–393. https://doi.org/10.1111/J.1751-0813.2011.00829.X
  2. Preston SA, Brown MP, Chmielewski TL, Trumble TN, Zimmel DN, Hernandez JA. Effects of yearling sale purchase price, exercise history, lameness, and athletic performance on purchase price of Thoroughbreds at 2‐year‐old in‐training sales. J Am Vet Med Assoc. 2012;241(11):1499–1504. https://doi.org/10.2460/JAVMA.241.11.1499
  3. Shelton AV, Tupper J, Bolt DM. Prejudicial findings regarding suitability for intended purpose during pre‐purchase examinations in a mixed horse population—a retrospective observational study in the United Kingdom. Equine Vet J. 2024;57(1):153–159. https://doi.org/10.1111/EVJ.14061
  4. Littman MP, Goldstein RE, Labato MA, Lappin MR, Moore GE. ACVIM small animal consensus statement on Lyme disease in dogs: diagnosis, treatment, and prevention. J Vet Intern Med. 2006;20(2):422–434. https://doi.org/10.1892/0891-6640(2006)20[422:ASACSO]2.0.CO;2
  5. Unlu AM, Andersen NS, Larsen SL, et al. Differentiating Lyme arthritis: a case‐based review. Rheumatol Int. 2024;44(11):2671–2678. https://doi.org/10.1007/S00296-024-05618-0/TABLES/3
  6. Roberts J, Merchant E. Trauma‐related Lyme arthritis. BMJ Case Rep. 2023;16(7):e255532. https://doi.org/10.1136/BCR-2023-255532
  7. Kim L, Lashnits E, Breitschwerdt EB, Elam A, Grade N, Miller J, et al. Antibodies to Borrelia burgdorferi and Bartonella species in serum and synovial fluid from people with rheumatic diseases. Microbiol Spectr. 2024;12:e0165323. https://doi.org/10.1128/spectrum.01653-23
  8. Corre C, Coiffier G, Le Goff B, et al. Lyme arthritis in Western Europe: a multicentre retrospective study. Eur J Clin Microbiol Infect Dis. 2022;41(1):21–27. https://doi.org/10.1007/S10096-021-04334-Y/FIGURES/3
  9. Lochhead RB, Strle K, Arvikar SL, Weis JJ, Steere AC. Lyme arthritis: linking infection, inflammation and autoimmunity. Nat Rev Rheumatol. 2021;17(8):449–461. https://doi.org/10.1038/S41584-021-00648-5
  10. Bowman KA, Wiggins CD, DeRiso E, Paul S, Strle K, Branda JA, et al. Borrelia‐specific antibody profiles and complement deposition in joint fluid distinguish antibiotic‐refractory from ‐responsive Lyme arthritis. iScience. 2024;27(2):108804. https://doi.org/10.1016/J.ISCI.2024.108804
  11. Tabar MD, Tabar J, Naranjo C, Altet L, Roura X. Detection of vector‐borne pathogens in owned dogs with cranial cruciate ligament rupture living in the Mediterranean area. Parasites Vectors. 2022;15(1):105. https://doi.org/10.1186/S13071-022-05205-X
  12. Muir P, Oldenhoff WE, Hudson AP, Manley PA, Schaefer SL, Markel MD, et al. Detection of DNA from a range of bacterial species in the knee joints of dogs with inflammatory knee arthritis and associated degenerative anterior cruciate ligament rupture. Microb Pathog. 2007;42(2–3):47–55. https://doi.org/10.1016/J.MICPATH.2006.10.002
  13. Burtis JC, Foster E, Schwartz AM, Kugeler KJ, Maes SE, Fleshman AC, et al. Predicting distributions of blacklegged ticks (Ixodes scapularis), Lyme disease spirochetes (Borrelia burgdorferi sensu stricto) and human Lyme disease cases in the eastern United States. Ticks Tick Borne Dis. 2022;13(5):102000. https://doi.org/10.1016/J.TTBDIS.2022.102000
  14. Jacob AE, Weese JS, Rosseau J, Clow KM. Spatial patterns of Borrelia burgdorferi, Borrelia miyamotoi and Anaplasma phagocytophilum detected in Ixodes spp. ticks from Canadian companion animals, 2019–2020. Zoonoses Public Health. 2022;69(8):944–955. https://doi.org/10.1111/ZPH.12992
  15. Funk RA, Pleasant RS, Witonsky SG, Reeder DS, Werre SR, Hodgson DR. Seroprevalence of Borrelia burgdorferi in horses presented for Coggins testing in Southwest Virginia and change in positive test results approximately 1 year later. J Vet Intern Med. 2016;30:1300–1304. https://doi.org/10.1111/jvim.13973
  16. Thompson D, Thirumalapura NR, Tewari D. Prevalence of Anaplasma phagocytophilum and Borrelia burgdorferi infection in horses from Pennsylvania (2017–2019) using antibody and organism‐based detection. J Am Vet Med Assoc. 2022;260(14):1834–1838. https://doi.org/10.2460/JAVMA.22.06.0232
  17. DeVilbiss BA, Mohammed HO, Divers TJ. Perception of equine practitioners regarding the occurrence of selected equine neurologic diseases in the northeast over a 10‐year period. J Equine Vet Sci. 2009;29(4):237–246. https://doi.org/10.1016/J.JEVS.2009.03.002
  18. Smarsh DN, Kenny LB, Spindler M, Poh KC, Machtinger ET. Knowledge and perception of equine ticks and tick‐borne diseases of Pennsylvania horse owners and caretakers. J Equine Vet Sci. 2024;139:105092. https://doi.org/10.1016/J.JEVS.2024.105092
  19. Swinebroad EL. Borreliosis in sport horse practice. Vet Clin North Am Equine Pract. 2018;34(2):313–343. https://doi.org/10.1016/J.CVEQ.2018.04.011
  20. Egenvall A, Franzén P, Gunnarsson A, Engvall EO, Vågsholm I, Wikström UB, et al. Cross‐sectional study of the seroprevalence to Borrelia burgdorferi sensu lato and granulocytic Ehrlichia spp. and demographic, clinical and tick‐exposure factors in Swedish horses. Prev Vet Med. 2001;49(3–4):191–208. https://doi.org/10.1016/S0167-5877(01)00187-8
  21. Divers TJ, Gardner RB, Madigan JE, Witonsky SG, Bertone JJ, Swinebroad EL, et al. Borrelia burgdorferi infection and Lyme disease in North American horses: a consensus statement. J Vet Intern Med. 2018;32(2):617–632. https://doi.org/10.1111/JVIM.15042
  22. Chang YF, Novosol V, Mcdonough SP, et al. Experimental infection of ponies with Borrelia burgdorferi by exposure to ixodid ticks. Vet Pathol. 2000;37(1):68–76. https://doi.org/10.1354/VP.37-1-68/ASSET/E8FDC856-9DC2-4AFA-9BDB-FB5C2EA9E1E8/ASSETS/IMAGES/LARGE/10.1354_VP.37-1-68-FIG5.JPG
  23. Pearson EK, Guarino C, Cercone M, Divers T, Lambert J, García‐López J, et al. Association of Borrelia burgdorferi with nuchal bursitis and elevated outer surface protein A–specific serum antibodies in horses of the northeastern United States. J Am Vet Med Assoc. 2024;262(11):1476–1484. https://doi.org/10.2460/JAVMA.24.05.0312
  24. Serpa PBS, Bogers S, Byron C, Cardona G, Patton M. Presumptive Lyme disease‐associated eosinophilic synovitis in a horse. J Equine Vet Sci. 2025;150:105595. https://doi.org/10.1016/J.JEVS.2025.105595
  25. Passamonti F, Veronesi F, Cappelli K, Capomaccio S, Reginato A, Miglio A, et al. Polysynovitis in a horse due to Borrelia burgdorferi sensu lato infection—case study. Ann Agric Environ Med. 2015;22(2):247–250. https://doi.org/10.5604/12321966.1152074
  26. Sipka A, Wagner B. Fluorescent bead–based multiplex assays improve serological disease diagnostics and have potential of identifying sensitive immune biomarkers for maintaining health and performance. J Am Vet Med Assoc. 2025;263(S1):S33–S44. https://doi.org/10.2460/JAVMA.24.11.0760
  27. Wagner B, Freer H, Rollins A, Erb HN, Lu Z, Gröhn Y. Development of a multiplex assay for the detection of antibodies to Borrelia burgdorferi in horses and its validation using Bayesian and conventional statistical methods. Vet Immunol Immunopathol. 2011;144:374–381. https://doi.org/10.1016/j.vetimm.2011.08.005
  28. Lyme Disease Multiplex Testing for Horses|Cornell University College of Veterinary Medicine. https://www.vet.cornell.edu/animal-health-diagnostic-center/testing/testing-protocols-interpretations/lyme-disease-multiplex-testing-horses
  29. Badawi A, Arora P, Brenner D. Biologic markers of antibiotic‐refractory Lyme arthritis in human: a systematic review. Infect Dis Ther. 2018;8(1):5. https://doi.org/10.1007/S40121-018-0223-0
  30. Brown CR, Blaho VA, Loiacono CM. Susceptibility to experimental Lyme arthritis correlates with KC and monocyte chemoattractant protein‐1 production in joints and requires neutrophil recruitment via CXCR2. J Immunol. 2003;171(2):893–901. https://doi.org/10.4049/JIMMUNOL.171.2.893
  31. Strle K, Shin JJ, Glickstein LJ, Steere AC. A toll‐like receptor 1 polymorphism is associated with heightened T‐helper 1 inflammatory responses and antibiotic‐refractory Lyme arthritis. Arthritis Rheum. 2012;64(5):1497. https://doi.org/10.1002/ART.34383
  32. Shin JJ, Strle K, Glickstein LJ, Luster AD, Steere AC. Borrelia burgdorferi stimulation of chemokine secretion by cells of monocyte lineage in patients with Lyme arthritis. Arthritis Res Ther. 2010;12(5):R168. https://doi.org/10.1186/AR3128
  33. Zhao Z, McCloud B, Fleming R, Klempner MS. Borrelia burgdorferi‐induced monocyte chemoattractant protein‐1 production in vivo and in vitro. Biochem Biophys Res Commun. 2007;358(2):528–533. https://doi.org/10.1016/J.BBRC.2007.04.150
  34. De Benedetti F, Pignatti P, Bernasconi S, et al. Interleukin 8 and monocyte chemoattractant protein‐1 in patients with juvenile rheumatoid arthritis. Relation to onset types, disease activity, and synovial fluid leukocytes. J Rheumatol. 1999;26(2):425–431.
  35. Hayashida K, Nanki T, Girschick H, Yavuz S, Ochi T, Lipsky PE. Synovial stromal cells from rheumatoid arthritis patients attract monocytes by producing MCP‐1 and IL‐8. Arthritis Res. 2001;3(2):118–126. https://doi.org/10.1186/AR149/FIGURES/8
  36. Appleton CTG, Usmani SE, Pest MA, Pitelka V, Mort JS, Beier F. Reduction in disease progression by inhibition of transforming growth factor A–CCL2 signaling in experimental posttraumatic osteoarthritis. Arthritis Rheumatol. 2015;67(10):2691–2701. https://doi.org/10.1002/ART.39255
  37. Münch S, Braun P, Wernery U, et al. Prevalence, serovars, phage types, and antibiotic susceptibilities of Salmonella strains isolated from animals in the United Arab Emirates from 1996 to 2009. Tropl Anim Health Prod. 2012;44(7):1725–1738. https://doi.org/10.1007/S11250-012-0130-4/FIGURES/3
  38. Li L, Jiang BE. Serum and synovial fluid chemokine ligand 2/monocyte chemoattractant protein 1 concentrations correlates with symptomatic severity in patients with knee osteoarthritis. Ann Clin Biochem. 2015;52(2):276–282. https://doi.org/10.1177/0004563214545117/ASSET/73334633-6CC4-43FD-A0A7-EE6EECC53C7A/ASSETS/IMAGES/LARGE/10.1177_0004563214545117-FIG4.JPG
  39. Miller RE, Tran PB, Das R, et al. CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis. Proc Natl Acad Sci U S A. 2012;109(50):20602–20607. https://doi.org/10.1073/PNAS.1209294110/SUPPL_FILE/PNAS.201209294SI.PDF
  40. Miotla Zarebska J, Chanalaris A, Driscoll C, Burleigh A, Miller RE, Malfait AM, et al. CCL2 and CCR2 regulate pain‐related behaviour and early gene expression in post‐traumatic murine osteoarthritis but contribute little to chondropathy. Osteoarthr Cartil. 2017;25(3):406–412. https://doi.org/10.1016/j.joca.2016.10.008
  41. Watkins A, Fasanello D, Stefanovski D, et al. 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;17(1):1–18. https://doi.org/10.1186/S12917-021-02873-2
  42. Ley C, Ekman S, Elmén A, Nilsson G, Eloranta ML. Interleukin‐6 and tumour necrosis factor in synovial fluid from horses with carpal joint pathology. J Vet Med Ser A. 2007;54(7):346–351. https://doi.org/10.1111/J.1439-0442.2007.00956.X
  43. Brown KA, Davidson EJ, Johnson AL, Wulster KB, Ortved K. Inflammatory cytokines in horses with cervical articular process joint osteoarthritis on standing cone beam computed tomography. Equine Vet J. 2021;53(5):944–954. https://doi.org/10.1111/EVJ.13392
  44. Bertuglia A, Pagliara E, Grego E, Ricci A, Brkljaca‐Bottegaro N. Pro‐inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career. BMC Vet Res. 2016;12(1):246. https://doi.org/10.1186/S12917-016-0873-7
  45. Straubinger RK, Straubinger AF, Harter L, et al. Borrelia burgdorferi migrates into joint capsules and causes an up‐regulation of interleukin‐8 in synovial membranes of dogs experimentally infected with ticks. Infect Immun. 1997;65(4):1273–1285. https://doi.org/10.1128/IAI.65.4.1273-1285.1997
  46. Shin JJ, Glickstein LJ, Steere AC. High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic‐refractory Lyme arthritis. Arthritis Rheum. 2007;56(4):1325–1335. https://doi.org/10.1002/ART.22441
  47. Parthasarathy G, Fevrier HB, Philipp MT. Non‐viable Borrelia burgdorferi induce inflammatory mediators and apoptosis in human oligodendrocytes. Neurosci Lett. 2013;556:200–203. https://doi.org/10.1016/j.neulet.2013.10.032
  48. Parthasarathy G, Gadila SKG. Neuropathogenicity of non‐viable Borrelia burgdorferi ex vivo. Sci Rep. 2022;12(1):688. https://doi.org/10.1038/S41598-021-03837-0
  49. Nardelli DT, Callister SM, Schell RF. Lyme arthritis: current concepts and a change in paradigm. Clin Vaccine Immunol. 2007;15(1):21. https://doi.org/10.1128/CVI.00330-07
  50. Wang G, Petzke MM, Iyer R, Wu H, Schwartz I. Pattern of proinflammatory cytokine induction in RAW264.7 mouse macrophages is identical for virulent and attenuated Borrelia burgdorferi. J Immunol. 2008;180(12):8306–8315. https://doi.org/10.4049/JIMMUNOL.180.12.8306
  51. Divers TJ, Mongodin EF, Miller CB, Belgrave RL, Gardner RB, Fraser CM, et al. Genomic hybrid capture assay to detect Borrelia burgdorferi: an application to diagnose neuroborreliosis in horses. J Vet Diagn Invest. 2022;34(5):909–912. https://doi.org/10.1177/10406387221112617
  52. Marre ML, Darcy CT, Yinh J, Akira S, Uematsu S, Steere AC, et al. Role of adrenomedullin in Lyme disease. Infect Immun. 2010;78(12):5307–5313. https://doi.org/10.1128/IAI.00630-10
  53. Melicherčík P, Mazura M, Hodík M, et al. Synovial fluid alpha‐defensins in Lyme arthritis—a useful marker. Folia Microbiol (Praha). 2024;69(6):1355–1362. https://doi.org/10.1007/S12223-024-01173-0/FIGURES/3
  54. Weinberg J. The antiinflammatory effects of tetracyclines. Cutis. 2005;75(4 Suppl):6–11.

Citations

This article has been cited 0 times.