{"doi":"10.1016/j.ard.2025.02.008","title":"The IL-6 axis in vascular inflammation: effects of IL-6 receptor blockade on vascular lesions from patients with giant-cell arteritis","abstract":null,"journal":"Annals of the Rheumatic Diseases","year":2025,"id":610884,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1570803,"name":"Farah Kamberovic","orcid":null,"position":1,"is_corresponding":false},{"id":1570804,"name":"Roser Alba-Rovira","orcid":"0000-0003-3308-5787","position":2,"is_corresponding":false},{"id":1570805,"name":"Ester Planas-Rigol","orcid":null,"position":3,"is_corresponding":false},{"id":384675,"name":"Sergio Prieto‐González","orcid":"0000-0003-3179-597X","position":4,"is_corresponding":false},{"id":1570806,"name":"Núria Farran-Centelles","orcid":null,"position":5,"is_corresponding":false},{"id":1570807,"name":"Ester Tobías","orcid":null,"position":6,"is_corresponding":false},{"id":1570808,"name":"Anna Jordán","orcid":null,"position":7,"is_corresponding":false},{"id":958703,"name":"Marco A. Alba","orcid":"0000-0002-4712-441X","position":8,"is_corresponding":false},{"id":512382,"name":"Eduard Quintana","orcid":"0000-0002-5386-7463","position":9,"is_corresponding":false},{"id":1570809,"name":"Georgina Espígol-Frigolé","orcid":null,"position":10,"is_corresponding":false},{"id":25197,"name":"María C. Cid","orcid":"0000-0002-4730-0938","position":11,"is_corresponding":false},{"id":1570802,"name":"Marc Corbera-Bellalta","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The IL-6 axis in vascular inflammation: effects of IL-6 receptor blockade on vascular lesions from patients with giant-cell arteritis","abstract":"Blocking interleukin (IL)-6-receptor with tocilizumab has been a major advance in the treatment of giant-cell arteritis (GCA), supporting a crucial role of IL-6 receptor signalling. However, nearly half of the patients are not able to maintain glucocorticoid- free remission with tocilizumab. The impact of tocilizumab on vascular lesions of GCA is largely unknown since conflicting results have been obtained by imaging. The expression and functional role of IL-6-receptor in GCA immunopathology has not been previously investigated. This study aimed to investigate expression of IL-6 receptor in GCA and control arteries and to assess the impact of tocilizumab on ex vivo-cultured temporal arteries and aortic tissue from patients with GCA.This study used a hypothesis-driven, candidate molecule transcriptomic approach using ex vivo temporal artery and aortic tissue culture, quantitative real-time polymerase chain reaction, immunofluorescence, Western Blot, immunoassay, adhesion, and chemotaxis assays.IL-6 receptor protein expressed intensively in GCA compared with that in control arteries. Tocilizumab decreased expression/phosphorylation of STAT3 and reduced expression of STAT3-dependent molecules including suppressor of cytokine signalling 3, CCL-2, and ICAM-1 in cultured GCA-involved arteries and patients' peripheral blood mononuclear cells (PBMCs). A similar trend was observed in aortic tissue. Consistently, tocilizumab reduced PBMC adhesiveness to vascular smooth muscle cells and human umbilical vein endothelial cells and chemotaxis towards supernatants of tocilizumab-treated GCA arteries. In some specimens, tocilizumab increased STAT1 phosphorylation and expression of STAT1-dependent chemokines including CXCL9 and CXCL10.Tocilizumab has a significant impact on vascular lesions by reducing, but not abrogating, key molecules involved in PBMC recruitment. About half of the patients may activate alternative inflammatory pathways in their lesions as a potential escape mechanism to tocilizumab that deserves further investigation.","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40074597","pmcid":null,"openalex_id":"https://openalex.org/W4408302405","authors":[],"funders":[{"funder_name":"H2020 Marie Skłodowska-Curie Actions","grant_id":"813545","title":"HEalth data LInkage for ClinicAL benefit"},{"funder_name":"Ministerio de Ciencia e Innovación","grant_id":"PID2020-114909RB-I00","title":null},{"funder_name":"Agència de Gestió d'Ajuts Universitaris i de Recerca","grant_id":"2021 SGR 01561","title":null}],"total_grants":3,"fwci":4.6789,"citation_percentile":0.94832686,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":3}],"oa_status":"closed","license":"Elsevier TDM","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0003496725002365?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0003496725002365?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.ard.2025.02.008","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40074597","host_type":"repository"}],"fields_of_study":["Vasculitis and related conditions","Otitis Media and Relapsing Polychondritis","Systemic Lupus Erythematosus Research","03 medical and health sciences","0302 clinical medicine","Humans","Giant Cell Arteritis","Antibodies, Monoclonal, Humanized","Receptors, Interleukin-6","Temporal Arteries","Male","Female","Aged","Aorta","Interleukin-6","Signal Transduction","Aged, 80 and over","STAT3 Transcription Factor","Middle Aged","Intercellular Adhesion Molecule-1","Cell Adhesion","Chemokine CCL2","Case-Control Studies"],"mesh_terms":["Aged","Aged, 80 and over","Aorta","Cell Adhesion","Female","Humans","Male","Middle Aged","Temporal Arteries","Giant Cell Arteritis","Signal Transduction","Interleukin-6","Case-Control Studies","Intercellular Adhesion Molecule-1","Chemokine CCL2","Receptors, Interleukin-6","STAT3 Transcription Factor","Antibodies, Monoclonal, Humanized"],"keywords":["Medicine","Giant cell arteritis","Arteritis","Blockade","Inflammation","Vasculitis","Pathology","Receptor","Immunology","Internal medicine","Male","Aged, 80 and over","STAT3 Transcription Factor","Interleukin-6","Middle Aged","Antibodies, Monoclonal, Humanized","Intercellular Adhesion Molecule-1","Receptors, Interleukin-6","Temporal Arteries","Case-Control Studies","Cell Adhesion","Humans","Female","Aorta","Chemokine CCL2","Aged","Signal Transduction"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-01T12:25:08.813898Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}