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Journal of veterinary pharmacology and therapeutics2002; 25(2); 145-153; doi: 10.1046/j.1365-2885.2002.00397.x

Effects of carprofen (R and S enantiomers and racemate) on the production of IL-1, IL-6 and TNF-alpha by equine chondrocytes and synoviocytes.

Abstract: Chondrocytes and synoviocytes harvested from the joints of healthy horses were maintained in tissue culture. Production of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in response to lipopolysaccharide (LPS), and the effects of addition of carprofen (racemate and R and S enantiomers) were determined. Lipopolysaccharide failed to stimulate TNF-alpha activity in both cell types but concentrations of IL-1 and IL-6 were both increased in a concentration and time-related manner. Both carprofen enantiomers and the racemic mixture attenuated the increase in IL-6 induced by LPS in synoviocytes, and S carprofen exerted a similar effect on chondrocytes. Neither enantiomer nor the racemate of carprofen suppressed the increase in IL-1 release produced by LPS in chondrocytes and synoviocytes. An action of carprofen to suppress IL-6 release might contribute to the actions which occur in vivo.
Publication Date: 2002-05-10 PubMed ID: 12000535DOI: 10.1046/j.1365-2885.2002.00397.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article explores the impact of carprofen enantiomers (R and S) and racemate on the production of certain cytokines (IL-1, IL-6, and TNF-alpha) by horse chondrocytes and synoviocytes in laboratory conditions. The study found that both carprofen structures and their mixture reduced the increase in IL-6 brought on by lipopolysaccharide in synoviocytes, with similar effects seen in chondrocytes from the S carprofen.

Chondrocyte and Synoviocyte Harvesting

  • The research initiated with collecting chondrocytes and synoviocytes from healthy horse joints.
  • The cells were then cultured in a laboratory setting to closely observe and interact with them.

Stimulating Cytokine Production

  • In order to elicit a response from the cells, they were then treated with lipopolysaccharide (LPS), a substance known to stimulate cytokine production.
  • Remarkably, LPS didn’t promote TNF-alpha activity in either cell type.
  • However, LPS did succeed in incrementing the concentrations of IL-1 and IL-6, and this increase occurred in a consistent and time-dependent manner.

Examining the Impact of Carprofen

  • The next phase involved introducing carprofen (both R and S enantiomers and their racemate) to the cells.
  • Both the R and S carprofen enantiomers, as well as their racemate, were seen to buffer the increased IL-6 brought on by LPS in synoviocytes.
  • The same inhibitory effect was observed in chondrocytes treated with S carprofen.

Lack of Impact on IL-1 Production

  • On the contrary, none of the carprofen forms were able to suppress the uprise in IL-1 release that was produced by the LPS in both chondrocytes and synoviocytes.

Potential In Vivo Effects

  • The study concludes by hypothesizing that carprofen’s observed suppression of IL-6 release could contribute to the real-world biological effects of the drug.

Cite This Article

APA
Armstrong S, Lees P. (2002). Effects of carprofen (R and S enantiomers and racemate) on the production of IL-1, IL-6 and TNF-alpha by equine chondrocytes and synoviocytes. J Vet Pharmacol Ther, 25(2), 145-153. https://doi.org/10.1046/j.1365-2885.2002.00397.x

Publication

ISSN: 0140-7783
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 25
Issue: 2
Pages: 145-153

Researcher Affiliations

Armstrong, S
  • Department of Veterinary Basic Sciences, The Royal Veterinary College, Hawkshead Campus, North Mymms, Hatfield, Herts AL9 7TA, UK.
Lees, P

    MeSH Terms

    • Animals
    • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
    • Anti-Inflammatory Agents, Non-Steroidal / chemistry
    • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
    • Carbazoles / administration & dosage
    • Carbazoles / chemistry
    • Carbazoles / pharmacology
    • Cell Line / drug effects
    • Cell Line / immunology
    • Chondrocytes / drug effects
    • Chondrocytes / immunology
    • Cytokines / biosynthesis
    • Dose-Response Relationship, Drug
    • Horses / immunology
    • Interleukin-1 / biosynthesis
    • Interleukin-6 / biosynthesis
    • Isomerism
    • Lipopolysaccharides / pharmacology
    • Synovial Fluid / cytology
    • Synovial Fluid / immunology
    • Tumor Necrosis Factor-alpha / biosynthesis

    Citations

    This article has been cited 6 times.
    1. Jacobs CC, Schnabel LV, McIlwraith CW, Blikslager AT. Non-steroidal anti-inflammatory drugs in equine orthopaedics. Equine Vet J 2022 Jan 25;54(4):636-48.
      doi: 10.1111/evj.13561pubmed: 35076950google scholar: lookup
    2. Hillström A, Bylin J, Hagman R, Björhall K, Tvedten H, Königsson K, Fall T, Kjelgaard-Hansen M. Measurement of serum C-reactive protein concentration for discriminating between suppurative arthritis and osteoarthritis in dogs. BMC Vet Res 2016 Oct 28;12(1):240.
      doi: 10.1186/s12917-016-0868-4pubmed: 27793205google scholar: lookup
    3. Andreassen SM, Berg LC, Nielsen SS, Kristensen AT, Jacobsen S. mRNA expression of genes involved in inflammation and haemostasis in equine fibroblast-like synoviocytes following exposure to lipopolysaccharide, fibrinogen and thrombin. BMC Vet Res 2015 Jun 27;11:141.
      doi: 10.1186/s12917-015-0448-zpubmed: 26116380google scholar: lookup
    4. Hish GA Jr, Diaz JA, Hawley AE, Myers DD Jr, Lester PA. Effects of analgesic use on inflammation and hematology in a murine model of venous thrombosis. J Am Assoc Lab Anim Sci 2014 Sep;53(5):485-93.
      pubmed: 25255071
    5. Lees P. Pharmacology of drugs used to treat osteoarthritis in veterinary practice. Inflammopharmacology 2003;11(4):385-99.
      doi: 10.1163/156856003322699564pubmed: 15035792google scholar: lookup
    6. Zhi J, Qiao K, Xie L, Pascottini OB, Opsomer G, Dong Q. The In Vitro Effects of Carprofen on Lipopolysaccharide-Induced Neutrophil Extracellular Trap Formation in Dairy Cows. Animals (Basel) 2024 Mar 21;14(6).
      doi: 10.3390/ani14060985pubmed: 38540082google scholar: lookup