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Tezepelumab decreas...
Tezepelumab decreases airway epithelial IL-33 and T2-inflammation in response to viral stimulation in patients with asthma
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- Sverrild, A. (author)
- Bispebjerg Hospital
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- Cerps, S. (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Nieto-Fontarigo, J. J. (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups,CIBER de Fisiopatología Obesidad y Nutricion (CIBEROBN),University of Santiago de Compostela,Health Research Institute of Santiago de Compostela (IDIS)
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- Ramu, S. (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Hvidtfeldt, M. (author)
- Bispebjerg Hospital
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- Menzel, M. (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Kearley, J. (author)
- AstraZeneca, UK
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- Griffiths, J. M. (author)
- AstraZeneca, UK
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- Parnes, J. R. (author)
- Amgen Inc.
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- Porsbjerg, C. (author)
- Bispebjerg Hospital
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- Uller, L. (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Respiratory Immunopharmacology,Lund University Research Groups
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(creator_code:org_t)
- English.
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In: Allergy: European Journal of Allergy and Clinical Immunology. - 0105-4538.
- Related links:
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
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- 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 (IFNβ, 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, IFNβ 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 IFNβ 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- airway epithelium
- asthma
- tezepelumab
- virus
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Sverrild, A.
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Cerps, S.
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Nieto-Fontarigo, ...
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Ramu, S.
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Hvidtfeldt, M.
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Menzel, M.
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show more...
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Kearley, J.
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Griffiths, J. M.
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Parnes, J. R.
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Porsbjerg, C.
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Uller, L.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Respiratory Medi ...
- Articles in the publication
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Allergy: Europea ...
- By the university
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Lund University