Interleukin (IL)-41, also known as Meteorin-like, is expressed in the synovial tissue of patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and osteoarthritis (OA), and is present and inducible in the enthesis, according to study results published in Clinical Immunology.
The study included data from patients who were treatment-naive. Researchers extracted synovial fluid and measured IL-41 levels using enzyme-linked immunosorbent assay; results from the synovial fluid had <10% reproducibility error. Cell cultures and receptor analysis by flow cytometry were performed to achieve appropriate samples. Researchers also obtained patient demographics.
Study results indicated that IL-41 was detectable in synovial fluid samples in patients with PsA, RA and OA, although it was significantly higher in PsA and RA compared with OA (median, 7722 pg/mL; P =.0011 and 8325 pg/mL; P =.0003 vs 5044 pg/mL, respectively). Researchers also obtained levels of IL-41 in synovial fluid from patients with gout; it was higher compared with IL-41 in patients with OA, but statistical significance was not achieved.
Researchers investigated the production of IL-41 in healthy enthesis samples and noted that although minimal IL-41 was produced from enthesis mononuclear cells, entheseal stromal cells produced a significant amount of IL-41 in comparison. Synovial fibroblasts also showed similar levels of IL-41 compared with entheseal stromal cells.
In addition, the researchers assessed whether IL-41 could be induced by disease relevant mediators, including tumor necrosis factor (TNF), IL-17A, and IL-17F. Results showed that when used alone, TNF, IL-17A, and IL-17F did not induce an increase in IL-41, but TNF with IL-17A or IL-17F led to a significant increase in IL-41 production. Study investigators observed similar results with synovial fibroblasts.
Overall, IL-41 was significantly elevated in the synovium and was induced from enthesis stromal cells in patients with PsA.
“The precise role of IL-41 in PsA immunopathogenesis requires further study,” the researchers concluded.
Bridgewood C, Russell T, Weedon H, et al. The novel cytokine Metrnl/IL-41 is elevated in psoriatic arthritis synovium and inducible from both entheseal and synovial fibroblasts. J Clin Immunol. 2019;208:108253.