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.
Supplementary Information
The online version contains supplementary material available at 10.1186/s13075-024-03372-z.