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Tezepelumab decreases airway epithelial IL-33 and T2-inflammation in response to viral stimulation in patients with asthma.
Sverrild, A; Cerps, S; Nieto-Fontarigo, J J; Ramu, S; Hvidtfeldt, M; Menzel, M; Kearley, J; Griffiths, J M; Parnes, J R; Porsbjerg, C; Uller, L.
Afiliación
  • Sverrild A; Department of Respiratory Medicine, University Hospital Bispebjerg, Copenhagen, Denmark.
  • Cerps S; Department of Experimental Medicine, Lund University, Lund, Sweden.
  • Nieto-Fontarigo JJ; Department of Experimental Medicine, Lund University, Lund, Sweden.
  • Ramu S; BioLympho Research group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
  • Hvidtfeldt M; Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
  • Menzel M; Department of Experimental Medicine, Lund University, Lund, Sweden.
  • Kearley J; Department of Respiratory Medicine, University Hospital Bispebjerg, Copenhagen, Denmark.
  • Griffiths JM; Department of Experimental Medicine, Lund University, Lund, Sweden.
  • Parnes JR; Bioscience, Research & Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
  • Porsbjerg C; Translational Science and Experimental Medicine, Research & Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
  • Uller L; Translational Medicine, Amgen, Thousand Oaks, California, USA.
Allergy ; 79(3): 656-666, 2024 Mar.
Article en En | MEDLINE | ID: mdl-37846599
BACKGROUND: Respiratory virus infections are main triggers of asthma exacerbations. Tezepelumab, an anti-TSLP mAb, reduces exacerbations in patients with asthma, but the effect of blocking TSLP on host epithelial resistance and tolerance to virus infection is not known. AIM: To examine effects of blocking TSLP in patients with asthma on host resistance (IFNß, IFNλ, and viral load) and on the airway epithelial inflammatory response to viral challenge. METHODS: Bronchoalveolar lavage fluid (BALF, n = 39) and bronchial epithelial cells (BECs) were obtained from patients with uncontrolled asthma before and after 12 weeks of tezepelumab treatment (n = 13) or placebo (n = 13). BECs were cultured in vitro and exposed to the viral infection mimic poly(I:C) or infected by rhinovirus (RV). Alarmins, T2- and pro-inflammatory cytokines, IFNß IFNλ, and viral load were analyzed by RT-qPCR and multiplex ELISA before and after stimulation. RESULTS: IL-33 expression in unstimulated BECs and IL-33 protein levels in BALF were reduced after 12 weeks of tezepelumab. Further, IL-33 gene and protein levels decreased in BECs challenged with poly(I:C) after tezepelumab whereas TSLP gene expression remained unaffected. Poly(I:C)-induced IL-4, IL-13, and IL-17A release from BECs was also reduced with tezepelumab whereas IFNß and IFNλ expression and viral load were unchanged. CONCLUSION: Blocking TSLP with tezepelumab in vivo in asthma reduced the airway epithelial inflammatory response including IL-33 and T2 cytokines to viral challenge without affecting anti-viral host resistance. Our results suggest that blocking TSLP stabilizes the bronchial epithelial immune response to respiratory viruses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Virosis / Anticuerpos Monoclonales Humanizados Límite: Humans Idioma: En Revista: Allergy Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Dinamarca
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Virosis / Anticuerpos Monoclonales Humanizados Límite: Humans Idioma: En Revista: Allergy Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Dinamarca