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Veterinary surgery : VS2021; 50(3); 641-649; doi: 10.1111/vsu.13582

Influence of clinical and experimental intra-articular inflammation on neutrophil gelatinase-associated lipocalin concentrations in horses.

Abstract: To investigate neutrophil gelatinase-associated lipocalin (NGAL) concentrations in serum and synovial fluid (SF) from horses with joint inflammation. Methods: Experimental studies and retrospective clinical study. Methods: Serum and SF samples were available from healthy horses (n = 19), clinical cases, and horses with experimental joint inflammation. Clinical cases included horses with (n = 10) or without (n = 10) septic arthritis. Experimental intra-articular inflammation was induced by lipopolysaccharide (LPS; n = 7, severe inflammation), lidocaine (n = 6, moderate inflammation), or mepivacaine (n = 6, mild inflammation). Methods: Availability of samples was based on approval from the local ethical committee and from the Danish Animal Experiments Inspectorate. Neutrophil gelatinase-associated lipocalin was measured with a previously validated enzyme-linked immunosorbent assay. Repeated-measurements one- and two-way analysis of variance and correlation analysis were used to analyze NGAL concentrations and white blood cell counts (WBC). Results: After injection of LPS or lidocaine, SF NGAL concentrations increased 343- (P = .0035) and 60-fold (P = .0038) relative to baseline, respectively. Serum NGAL also increased in both groups (P < .05) but to lower concentrations than in SF. Concentrations were higher after injection of lidocaine SF NGAL than after injection of mepivacaine (P < .05) at 6 and 12 hours. Synovial fluid concentrations of NGAL were higher in horses with septic arthritis than in the nonseptic group (P = .0070) and in healthy controls (P = .0071). Concentrations of NGAL correlated with WBC in SF (P < .0001, R = 0.49) and in blood (P = .0051, R = 0.27). Conclusions: Neutrophil gelatinase-associated lipocalin concentrations increased in SF in response to experimentally induced and naturally occurring joint inflammation. Synovial fluid NGAL concentration correlated with WBC and, thus, seems to reflect intensity of joint inflammation. Conclusions: Neutrophil gelatinase-associated lipocalin may prove to be a useful biomarker of joint inflammation and infection in horses.
© 2021 The Authors. Veterinary Surgery published by Wiley Periodicals LLC. on behalf of American College of Veterinary Surgeons.
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Publication Date: 2021-01-31 PubMed ID: 33522003PubMed Central: PMC8048826DOI: 10.1111/vsu.13582Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The article discusses a research study that explores the levels of neutrophil gelatinase-associated lipocalin (NGAL) in blood and synovial fluid of horses suffering from joint inflammation. The researchers concluded that NGAL could serve as a helpful biomarker for detecting joint inflammation and infection in horses.

Research Methodology

  • The research involved both experimental studies and a retrospective clinical study. The subjects included healthy horses, clinical cases, and those with experimental joint inflammation.
  • Clinical cases were further classified into horses with septic arthritis and those without.
  • Joint inflammation was experimentally induced using lipopolysaccharide (LPS) for severe inflammation, lidocaine for moderate inflammation, or mepivacaine for mild inflammation.
  • The availability of serum and synovial fluid samples was approved by the local ethical committee and the Danish Animal Experiments Inspectorate.
  • The NGAL levels were measured using an enzyme-linked immunosorbent assay.
  • Data analysis was done using repeated-measurements one- and two-way analysis of variance and correlation analysis to interpret NGAL concentrations and white blood cell (WBC) counts.

Findings

  • After inducing inflammation with LPS or lidocaine, a significant spike was observed in the synovial fluid NGAL concentration.
  • These injections also caused an increase in serum NGAL levels but not as much as in synovial fluid.
  • In treatment with lidocaine, NGAL concentration was higher compared to mepivacaine.
  • Horses suffering from septic arthritis showed higher synovial fluid NGAL levels than those in the non-septic group and in healthy controls.
  • Concentrations of NGAL had significant relation with WBC in synovial fluid and blood.

Conclusion

  • Both the experimentally induced inflammation and naturally occurring joint inflammation led to an increase in NGAL levels in synovial fluid.
  • The correlation of NGAL concentration with WBC indicated that the former could be representative of the intensity of joint inflammation.
  • These research findings suggest that NGAL might be a potential biomarker to detect joint inflammation and infection in horses.

Cite This Article

APA
Frydendal C, Nielsen KB, Berg LC, van Galen G, Adler DMT, Andreassen SM, Jacobsen S. (2021). Influence of clinical and experimental intra-articular inflammation on neutrophil gelatinase-associated lipocalin concentrations in horses. Vet Surg, 50(3), 641-649. https://doi.org/10.1111/vsu.13582

Publication

Veterinary surgery : VS
ISSN: 1532-950X
NlmUniqueID: 8113214
Country: United States
Language: English
Volume: 50
Issue: 3
Pages: 641-649

Researcher Affiliations

Frydendal, Catina
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nielsen, Katrine B
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
Berg, Lise C
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
van Galen, Gaby
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
Adler, Ditte M T
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
Andreassen, Stine M
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jacobsen, Stine
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.

MeSH Terms

  • Animals
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Female
  • Horse Diseases / chemically induced
  • Horse Diseases / metabolism
  • Horses
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / veterinary
  • Joint Diseases / chemically induced
  • Joint Diseases / metabolism
  • Joint Diseases / veterinary
  • Lidocaine / adverse effects
  • Lipocalin-2 / blood
  • Lipocalin-2 / cerebrospinal fluid
  • Lipocalin-2 / metabolism
  • Lipopolysaccharides / adverse effects
  • Male
  • Mepivacaine / adverse effects
  • Retrospective Studies

Grant Funding

  • N/A / Foreningen KUSTOS af 1881

Conflict of Interest Statement

The authors declare no conflicts of interest related to this report.

References

This article includes 35 references
  1. Adkins AR. Establishing a diagnosis of septic arthritis/osteomyelitis—a challenging process. Equine Vet Educ 2012;24:615‐617.
  2. Gilbertie JM, Schnabel LV, Stefanovski D, Kelly DJ, Jacob ME, Schaer TP. Gram-negative multi-drug resistant bacteria influence survival to discharge for horses with septic synovial structures: 206 Cases (2010-2015).. Vet Microbiol 2018 Nov;226:64-73.
    pubmed: 30389045doi: 10.1016/j.vetmic.2018.10.009google scholar: lookup
  3. Ludwig EK, van Harreveld PD. Equine Wounds over Synovial Structures.. Vet Clin North Am Equine Pract 2018 Dec;34(3):575-590.
    pubmed: 30447770doi: 10.1016/j.cveq.2018.07.002google scholar: lookup
  4. Haltmayer E, Schwendenwein I, Licka TF. Course of serum amyloid A (SAA) plasma concentrations in horses undergoing surgery for injuries penetrating synovial structures, an observational clinical study.. BMC Vet Res 2017 May 22;13(1):137.
    pmc: PMC5441074pubmed: 28532514doi: 10.1186/s12917-017-1057-9google scholar: lookup
  5. Kjelgaard-Hansen M, Jacobsen S. Assay validation and diagnostic applications of major acute-phase protein testing in companion animals.. Clin Lab Med 2011 Mar;31(1):51-70.
    pubmed: 21295722doi: 10.1016/j.cll.2010.10.002google scholar: lookup
  6. Jacobsen S, Thomsen MH, Nanni S. Concentrations of serum amyloid A in serum and synovial fluid from healthy horses and horses with joint disease.. Am J Vet Res 2006 Oct;67(10):1738-42.
    pubmed: 17014325doi: 10.2460/ajvr.67.10.1738google scholar: lookup
  7. Sanchez-Teran AF, Bracamonte JL, Hendrick S, Burguess HJ, Duke-Novakovski T, Schott M, Hoff B, Rubio-Martínez LM. Effect of Arthroscopic Lavage on Systemic and Synovial Fluid Serum Amyloid A in Healthy Horses.. Vet Surg 2016 Feb;45(2):223-30.
    pubmed: 26767549doi: 10.1111/vsu.12439google scholar: lookup
  8. Sanchez Teran AF, Rubio-Martinez LM, Villarino NF, Sanz MG. Effects of repeated intra-articular administration of amikacin on serum amyloid A, total protein and nucleated cell count in synovial fluid from healthy horses.. Equine Vet J Suppl 2012 Dec;(43):12-6.
    pubmed: 23447871doi: 10.1111/j.2042-3306.2012.00637.xgoogle scholar: lookup
  9. Jacobsen S, Niewold TA, Halling-Thomsen M, Nanni S, Olsen E, Lindegaard C, Andersen PH. Serum amyloid A isoforms in serum and synovial fluid in horses with lipopolysaccharide-induced arthritis.. Vet Immunol Immunopathol 2006 Apr 15;110(3-4):325-30.
    pubmed: 16337010doi: 10.1016/j.vetimm.2005.10.012google scholar: lookup
  10. Ludwig EK, Brandon Wiese R, Graham MR, Tyler AJ, Settlage JM, Werre SR, Petersson-Wolfe CS, Kanevsky-Mullarky I, Dahlgren LA. Serum and Synovial Fluid Serum Amyloid A Response in Equine Models of Synovitis and Septic Arthritis.. Vet Surg 2016 Oct;45(7):859-867.
    pubmed: 27580707doi: 10.1111/vsu.12531google scholar: lookup
  11. Schwartz D, Pusterla N, Jacobsen S, Christopher MM. Analytical validation of a new point-of-care assay for serum amyloid A in horses.. Equine Vet J 2018 Sep;50(5):678-683.
    pubmed: 29344980doi: 10.1111/evj.12807google scholar: lookup
  12. Sanchez-Teran AF, Bracamonte JL, Hendrick S, Riddell L, Musil K, Hoff B, Rubio-Martínez LM. Effect of repeated through-and-through joint lavage on serum amyloid A in synovial fluid from healthy horses.. Vet J 2016 Apr;210:30-3.
    pubmed: 26831179doi: 10.1016/j.tvjl.2016.01.001google scholar: lookup
  13. Lindegaard C, Gleerup KB, Thomsen MH, Martinussen T, Jacobsen S, Andersen PH. Anti-inflammatory effects of intra-articular administration of morphine in horses with experimentally induced synovitis.. Am J Vet Res 2010 Jan;71(1):69-75.
    pubmed: 20043783doi: 10.2460/ajvr.71.1.69google scholar: lookup
  14. Makris K, Rizos D, Kafkas N, Haliassos A. Neurophil gelatinase-associated lipocalin as a new biomarker in laboratory medicine.. Clin Chem Lab Med 2012;50(9):1519-32.
    pubmed: 23104835doi: 10.1515/cclm-2012-0227google scholar: lookup
  15. Kjeldsen L, Bainton DF, Sengeløv H, Borregaard N. Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils.. Blood 1994 Feb 1;83(3):799-807.
    pubmed: 8298140
  16. Kjeldsen L, Johnsen AH, Sengeløv H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase.. J Biol Chem 1993 May 15;268(14):10425-32.
    pubmed: 7683678
  17. Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, Buemi M. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage.. Am J Kidney Dis 2008 Sep;52(3):595-605.
    pubmed: 18725016doi: 10.1053/j.ajkd.2008.01.020google scholar: lookup
  18. Xiao X, Yeoh BS, Vijay-Kumar M. Lipocalin 2: An Emerging Player in Iron Homeostasis and Inflammation.. Annu Rev Nutr 2017 Aug 21;37:103-130.
    pubmed: 28628361doi: 10.1146/annurev-nutr-071816-064559google scholar: lookup
  19. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery.. Lancet 2005 Apr 2-8;365(9466):1231-8.
    pubmed: 15811456doi: 10.1016/s0140-6736(05)74811-xgoogle scholar: lookup
  20. Saleh NY, Abo El Fotoh WMM, El-Hawy MA. Serum Neutrophil Gelatinase-Associated Lipocalin: A Diagnostic Marker in Pediatric Sepsis.. Pediatr Crit Care Med 2017 Jun;18(6):e245-e252.
    pubmed: 28445241doi: 10.1097/pcc.0000000000001186google scholar: lookup
  21. Mårtensson J, Bell M, Oldner A, Xu S, Venge P, Martling CR. Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury.. Intensive Care Med 2010 Aug;36(8):1333-40.
    pubmed: 20397003doi: 10.1007/s00134-010-1887-4google scholar: lookup
  22. Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Parvizi J. Diagnosing periprosthetic joint infection: has the era of the biomarker arrived?. Clin Orthop Relat Res 2014 Nov;472(11):3254-62.
    pmc: PMC4182392pubmed: 24590839doi: 10.1007/s11999-014-3543-8google scholar: lookup
  23. Bläser J, Triebel S, Tschesche H. A sandwich enzyme immunoassay for the determination of neutrophil lipocalin in body fluids.. Clin Chim Acta 1995 Mar 31;235(2):137-45.
    pubmed: 7554268doi: 10.1016/0009-8981(95)06020-7google scholar: lookup
  24. Gupta K, Shukla M, Cowland JB, Malemud CJ, Haqqi TM. Neutrophil gelatinase-associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9.. Arthritis Rheum 2007 Oct;56(10):3326-35.
    pubmed: 17907186doi: 10.1002/art.22879google scholar: lookup
  25. Katano M, Okamoto K, Arito M, Kawakami Y, Kurokawa MS, Suematsu N, Shimada S, Nakamura H, Xiang Y, Masuko K, Nishioka K, Yudoh K, Kato T. Implication of granulocyte-macrophage colony-stimulating factor induced neutrophil gelatinase-associated lipocalin in pathogenesis of rheumatoid arthritis revealed by proteome analysis.. Arthritis Res Ther 2009;11(1):R3.
    pmc: PMC2688233pubmed: 20527084doi: 10.1186/ar2587google scholar: lookup
  26. Jacobsen S, Berg LC, Tvermose E, Laurberg MB, van Galen G. Validation of an ELISA for detection of neutrophil gelatinase-associated lipocalin (NGAL) in equine serum.. Vet Clin Pathol 2018 Dec;47(4):603-607.
    pubmed: 30403420doi: 10.1111/vcp.12670google scholar: lookup
  27. Van Galen G, Jacobsen S, Vinther AM. NGAL: a new biomarker in the horse for renal injury and inflammation. J Vet Intern Med 2019;33:1549‐1549.
  28. Andreassen SM, Vinther AML, Nielsen SS, Andersen PH, Tnibar A, Kristensen AT, Jacobsen S. Changes in concentrations of haemostatic and inflammatory biomarkers in synovial fluid after intra-articular injection of lipopolysaccharide in horses.. BMC Vet Res 2017 Jun 19;13(1):182.
    pmc: PMC5477303pubmed: 28629364doi: 10.1186/s12917-017-1089-1google scholar: lookup
  29. Adler DMT, Serteyn D, Franck T, Jørgensen E, Christophersen MT, Denwood M, Verwilghen DR. Effects of intra-articular administration of lidocaine, mepivacaine, and the preservative methyl parahydroxybenzoate on synovial fluid biomarkers of horses.. Am J Vet Res 2020 Jun;81(6):479-487.
    pubmed: 32436793doi: 10.2460/ajvr.81.6.479google scholar: lookup
  30. Shashidharamurthy R, Machiah D, Aitken JD, Putty K, Srinivasan G, Chassaing B, Parkos CA, Selvaraj P, Vijay-Kumar M. Differential role of lipocalin 2 during immune complex-mediated acute and chronic inflammation in mice.. Arthritis Rheum 2013 Apr;65(4):1064-73.
    pmc: PMC3618508pubmed: 23280250doi: 10.1002/art.37840google scholar: lookup
  31. Hokamp JA, Nabity MB. Renal biomarkers in domestic species.. Vet Clin Pathol 2016 Mar;45(1):28-56.
    pubmed: 26918420doi: 10.1111/vcp.12333google scholar: lookup
  32. Conde J, Lazzaro V, Scotece M, Abella V, Villar R, López V, Gonzalez-Gay MÁ, Pino J, Gómez R, Mera A, Gualillo O. Corticoids synergize with IL-1 in the induction of LCN2.. Osteoarthritis Cartilage 2017 Jul;25(7):1172-1178.
    pubmed: 28185846doi: 10.1016/j.joca.2017.01.017google scholar: lookup
  33. Choi WS, Chun JS. Upregulation of lipocalin-2 (LCN2) in osteoarthritic cartilage is not necessary for cartilage destruction in mice.. Osteoarthritis Cartilage 2017 Mar;25(3):401-405.
    pubmed: 27477830doi: 10.1016/j.joca.2016.07.009google scholar: lookup
  34. Pedersen KR, Ravn HB, Hjortdal VE, Nørregaard R, Povlsen JV. Neutrophil gelatinase-associated lipocalin (NGAL): validation of commercially available ELISA.. Scand J Clin Lab Invest 2010 Sep;70(5):374-82.
    pubmed: 20509756doi: 10.3109/00365513.2010.486868google scholar: lookup
  35. Schuh MP, Nehus E, Ma Q, Haffner C, Bennett M, Krawczeski CD, Devarajan P. Long-term Stability of Urinary Biomarkers of Acute Kidney Injury in Children.. Am J Kidney Dis 2016 Jan;67(1):56-61.
    pmc: PMC4663180pubmed: 26032628doi: 10.1053/j.ajkd.2015.04.040google scholar: lookup

Citations

This article has been cited 5 times.
  1. Laurberg M, Saegerman C, Jacobsen S, Berg LC, Laursen SH, Hoeberg E, Sånge EA, van Galen G. Use of admission serum neutrophil gelatinase-associated lipocalin (NGAL) concentrations as a marker of sepsis and outcome in neonatal foals. PLoS One 2023;18(5):e0285819.
    doi: 10.1371/journal.pone.0285819pubmed: 37200285google scholar: lookup
  2. Jacobsen S, Mortensen CD, Høj EA, Vinther AM, Berg LC, Adler DMT, Verwilghen D, van Galen G. Neutrophil Gelatinase-Associated Lipocalin in Synovial Fluid from Horses with and without Septic Arthritis. Animals (Basel) 2022 Dec 21;13(1).
    doi: 10.3390/ani13010029pubmed: 36611638google scholar: lookup
  3. Galen GV, Olsen E, Siwinska N. Biomarkers of Kidney Disease in Horses: A Review of the Current Literature. Animals (Basel) 2022 Oct 5;12(19).
    doi: 10.3390/ani12192678pubmed: 36230418google scholar: lookup
  4. Poulsen AS, Stisen ZR, Skougaard M, Christensen R, Overgaard A, Gudbergsen H, Jacobsen S, Balslev-Clausen AP, Henriksen M, Kristensen LE, Bliddal H. Effect of weight loss and liraglutide on neutrophil gelatinase-associated lipocalin levels among individuals with overweight and knee osteoarthritis: Exploratory analyses of a randomized controlled trial. Osteoarthr Cartil Open 2025 Mar;7(1):100562.
    doi: 10.1016/j.ocarto.2024.100562pubmed: 39877802google scholar: lookup
  5. Bundgaard L, Årman F, Åhrman E, Walters M, Auf dem Keller U, Malmström J, Jacobsen S. An Equine Protein Atlas Highlights Synovial Fluid Proteome Dynamics during Experimentally LPS-Induced Arthritis. J Proteome Res 2024 Nov 1;23(11):4849-4863.
    doi: 10.1021/acs.jproteome.4c00125pubmed: 39395021google scholar: lookup
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