Annals of the Rheumatic Diseases, Journal Year: 2025, Volume and Issue: unknown
Published: March 1, 2025
Blocking interleukin (IL)-6-receptor with tocilizumab has been a major advance in the treatment of giant-cell arteritis (GCA), supporting crucial role IL-6 receptor signalling. However, nearly half patients are not able to maintain glucocorticoid- free remission tocilizumab. The impact on vascular lesions GCA is largely unknown since conflicting results have obtained by imaging. expression and functional IL-6-receptor immunopathology previously investigated. This study aimed investigate control arteries assess ex vivo-cultured temporal aortic tissue from GCA. used hypothesis-driven, candidate molecule transcriptomic approach using vivo artery culture, quantitative real-time polymerase chain reaction, immunofluorescence, Western Blot, immunoassay, adhesion, chemotaxis assays. protein expressed intensively compared that arteries. Tocilizumab decreased expression/phosphorylation STAT3 reduced STAT3-dependent molecules including suppressor cytokine signalling 3, CCL-2, ICAM-1 cultured GCA-involved patients' peripheral blood mononuclear cells (PBMCs). A similar trend was observed tissue. Consistently, PBMC adhesiveness smooth muscle human umbilical vein endothelial towards supernatants tocilizumab-treated In some specimens, increased STAT1 phosphorylation STAT1-dependent chemokines CXCL9 CXCL10. significant reducing, but abrogating, key involved recruitment. About may activate alternative inflammatory pathways their as potential escape mechanism deserves further investigation.
Language: Английский