Arthritis Research & Therapy (Jul 2024)

IL-40 is up-regulated in the synovial fluid and cartilage of osteoarthritis patients and contributes to the alteration of chondrocytes phenotype in vitro

  • L. Andrés Cerezo,
  • A. Navrátilová,
  • M. Kuklová,
  • A. Prokopcová,
  • J. Baloun,
  • T. Kropáčková,
  • D. Veigl,
  • S. Popelka,
  • P. Fulín,
  • R. Ballay,
  • K. Pavelka,
  • J. Vencovský,
  • L. Šenolt

DOI
https://doi.org/10.1186/s13075-024-03372-z
Journal volume & issue
Vol. 26, no. 1
pp. 1 – 7

Abstract

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Abstract Introduction IL-40 is a novel cytokine associated with autoimmune connective tissue disorders such as rheumatoid arthritis (RA) or Sjögren syndrome. We have previously shown an accumulation of IL-40 in the RA joint and its expression by immune cells and fibroblasts. Therefore, we aimed to assess the role of IL-40 in association with hyaline cartilage and chondrocyte activity. Methods Immunohistochemistry was employed to detect IL-40 in paired samples of loaded and unloaded regions of osteoarthritis (OA) cartilage (n=5). Synovial fluid IL-40 was analysed by ELISA in OA (n=31) and control individuals after knee injury (n=34). The impact of IL-40 on chondrocytes was tested in vitro. Results IL-40 was found in chondrocytes of the superficial zone of the OA cartilage, both in loaded and unloaded explants. Additionally, only biopsies from loaded explants showed significant IL-40 positivity in transitional zone chondrocytes. Levels of IL-40 were significantly elevated in the synovial fluid from OA patients compared to controls (p<0.0009) and correlated with synovial fluid leukocyte counts in OA (r=0.444, p=0.014). Chondrocytes exposed to IL-40 dose dependently increased in the secretion of pro-inflammatory cytokines IL-6 (p<0.0001) and IL-8 (p=0.004). Moreover, a dose dependent up-regulation of matrix degrading metalloproteinases MMP-1 (p=0.004), MMP-3 (p=0.031) and MMP-13 (p=0.0002) upon IL-40 treatment was observed in contrast to untreated chondrocytes. Conclusion This study is the first to demonstrate the accumulation of IL-40 in OA cartilage and its up-regulation in the synovial fluid of OA patients compared to controls. In addition, extracellular IL-40 appears to play a role in promoting inflammation and cartilage destruction by driving chondrocyte behaviour towards a more aggressive phenotype.

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