title: IL-6 blockade reverses the abnormal STAT activation of peripheral blood leukocytes from rheumatoid arthritis patients.
abstract: Considering the interplay of multiple STATs in response to cytokines, we investigated how IL-6 and its blocking affect STAT signaling in rheumatoid arthritis (RA). Leukocytes obtained from RA patients before and after tocilizumab treatment and healthy donors (HDs) were cytokine-stimulated and STAT phosphorylation was analyzed by cytometry. RA patients had significantly fewer pSTAT1+, pSTAT3+, and pSTAT6+ monocytes and pSTAT5+ lymphocytes than HDs. After 24weeks of treatment, percentages of IFNγ-induced pSTAT1+ and IL-10-induced pSTAT3+ monocytes in RA patients increased, reaching levels comparable to HDs. pSTAT1+ and pSTAT3+ cells correlated inversely with RA disease activity index and levels of pSTAT+ cells at baseline were higher in patients with good EULAR response to tocilizumab. IFNγ-induced pSTAT1+ cells correlated inversely with memory T cells and anti-CCP levels. IL-10-induced pSTAT3+ cells correlated with Treg/Teff ratio. Our findings suggest that IL-6 blocking reduces the inflammatory mechanisms through the correction of STAT1 and STAT3 activation status.
authors.affiliation: IIB-Institut Recerca Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Ortiz
authors.affiliation: Unit of Rheumatology, Department of Internal Medicine, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Diaz-Torné
authors.affiliation: Arthritis Unit, Rheumatology Department, Hospital Clinic, Barcelona, Spain.
authors.forename: M V
authors.initials: MV
authors.lastname: Hernández
authors.affiliation: Department of Rheumatology, Hospital Moises Broggi, Sant Joan Despí, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Reina
authors.affiliation: Department of Rheumatology, Hospital de Viladecans, Viladecans, Spain.
authors.forename: D
authors.initials: D
authors.lastname: de la Fuente
authors.affiliation: Department of Rheumatology, Hospital Comarcal de l'Alt Penedes, Vilafranca del Penedes, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Castellví
authors.affiliation: Unit of Rheumatology, Department of Internal Medicine, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Moya
authors.affiliation: Department of Rheumatology, Hospital de Viladecans, Viladecans, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Ruiz
authors.affiliation: Department of Rheumatology, Hospital Moises Broggi, Sant Joan Despí, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Corominas
authors.affiliation: IIB-Institut Recerca Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Zamora
authors.affiliation: IIB-Institut Recerca Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Cantó
authors.affiliation: Arthritis Unit, Rheumatology Department, Hospital Clinic, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Sanmartí
authors.affiliation: Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Juarez
authors.affiliation: IIB-Institut Recerca Hospital de la Santa Creu I Sant Pau, Barcelona, Spain. Electronic address: svidal@santpau.cat.
authors.forename: S
authors.initials: S
authors.lastname: Vidal
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D010456:Peptides, Cyclic; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors; C494079:STAT1 protein, human; C494086:STAT3 protein, human; C487763:cyclic citrullinated peptide; C502936:tocilizumab
keywords: IL-6; Leukocytes; Rheumatoid arthritis; STATs; Tocilizumab