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Arthritis Res Ther ; 26(1): 146, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080724

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.


Subject(s)
Chondrocytes , Interleukins , Osteoarthritis , Synovial Fluid , Adult , Aged , Female , Humans , Male , Middle Aged , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Cells, Cultured , Chondrocytes/metabolism , Chondrocytes/pathology , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Osteoarthritis/metabolism , Osteoarthritis/pathology , Phenotype , Synovial Fluid/metabolism , Up-Regulation , Interleukins/metabolism
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