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Anti-IL-5 treatment, but not neutrophil interference, attenuates inflammation in a mixed granulocytic asthma mouse model, elicited by air pollution

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Abstract
IntroductionDiesel exhaust particles (DEP) have been proven to aggravate asthma pathogenesis. We previously demonstrated that concurrent exposure to house dust mite (HDM) and DEP in mice increases both eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) and also results in higher levels of neutrophil-recruiting chemokines and neutrophil extracellular trap (NET) formation compared to sole HDM, sole DEP or saline exposure. We aimed to evaluate whether treatment with anti-IL-5 can alleviate the asthmatic features in this mixed granulocytic asthma model. Moreover, we aimed to unravel whether neutrophils modulate the DEP-aggravated eosinophilic airway inflammation.Material and methodsFemale C57BL6/J mice were intranasally exposed to saline or HDM and DEP for 3 weeks (subacute model). Interference with eosinophils was performed by intraperitoneal administration of anti-IL-5 (TRFK5), which neutralizes IL-5. Interference with neutrophils and neutrophil elastase was performed by intraperitoneal anti-Ly6G and sivelestat administration, respectively. Outcome parameters included eosinophils subsets (homeostatic EOS and inflammatory EOS), proinflammatory cytokines, goblet cell hyperplasia and airway hyperresponsiveness.ResultsThe administration of anti-IL-5 significantly decreased eosinophilic responses, affecting both inflammatory and homeostatic eosinophil subsets, upon subacute HDM + DEP exposure while BAL neutrophils, NET formation and other asthma features remained present. Neutrophils were significantly reduced after anti-Ly6G administration in BALF, lung and blood without affecting the eosinophilic inflammation upon HDM + DEP exposure. Sivelestat treatment tended to decrease BALF inflammation, including eosinophils, upon HDM + DEP exposure, but did not affect lung inflammation.ConclusionInhibition of IL-5 signalling, but not neutrophil interventions, significantly attenuates eosinophilic inflammation in a mouse model of mixed granulocytic asthma, elicited by air pollution exposure.
Keywords
asthma, air pollution, inflammation

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MLA
De Volder, Joyceline, et al. “Anti-IL-5 Treatment, but Not Neutrophil Interference, Attenuates Inflammation in a Mixed Granulocytic Asthma Mouse Model, Elicited by Air Pollution.” RESPIRATORY RESEARCH, vol. 26, no. 1, 2025, doi:10.1186/s12931-024-03082-9.
APA
De Volder, J., Bontinck, A., Haelterman, V., Boon, L., Joos, G., Brusselle, G., & Maes, T. (2025). Anti-IL-5 treatment, but not neutrophil interference, attenuates inflammation in a mixed granulocytic asthma mouse model, elicited by air pollution. RESPIRATORY RESEARCH, 26(1). https://doi.org/10.1186/s12931-024-03082-9
Chicago author-date
De Volder, Joyceline, Annelies Bontinck, Valerie Haelterman, Louis Boon, Guy Joos, Guy Brusselle, and Tania Maes. 2025. “Anti-IL-5 Treatment, but Not Neutrophil Interference, Attenuates Inflammation in a Mixed Granulocytic Asthma Mouse Model, Elicited by Air Pollution.” RESPIRATORY RESEARCH 26 (1). https://doi.org/10.1186/s12931-024-03082-9.
Chicago author-date (all authors)
De Volder, Joyceline, Annelies Bontinck, Valerie Haelterman, Louis Boon, Guy Joos, Guy Brusselle, and Tania Maes. 2025. “Anti-IL-5 Treatment, but Not Neutrophil Interference, Attenuates Inflammation in a Mixed Granulocytic Asthma Mouse Model, Elicited by Air Pollution.” RESPIRATORY RESEARCH 26 (1). doi:10.1186/s12931-024-03082-9.
Vancouver
1.
De Volder J, Bontinck A, Haelterman V, Boon L, Joos G, Brusselle G, et al. Anti-IL-5 treatment, but not neutrophil interference, attenuates inflammation in a mixed granulocytic asthma mouse model, elicited by air pollution. RESPIRATORY RESEARCH. 2025;26(1).
IEEE
[1]
J. De Volder et al., “Anti-IL-5 treatment, but not neutrophil interference, attenuates inflammation in a mixed granulocytic asthma mouse model, elicited by air pollution,” RESPIRATORY RESEARCH, vol. 26, no. 1, 2025.
@article{01JQ8TE7V1NHX52CG8XPHNWFZF,
  abstract     = {{IntroductionDiesel exhaust particles (DEP) have been proven to aggravate

 asthma pathogenesis. We previously demonstrated that concurrent exposure

 to house dust mite (HDM) and DEP in mice increases both eosinophils and

 neutrophils in bronchoalveolar lavage fluid (BALF) and also results in

 higher levels of neutrophil-recruiting chemokines and neutrophil

 extracellular trap (NET) formation compared to sole HDM, sole DEP or

 saline exposure. We aimed to evaluate whether treatment with anti-IL-5

 can alleviate the asthmatic features in this mixed granulocytic asthma

 model. Moreover, we aimed to unravel whether neutrophils modulate the

 DEP-aggravated eosinophilic airway inflammation.Material and

 methodsFemale C57BL6/J mice were intranasally exposed to saline or HDM

 and DEP for 3 weeks (subacute model). Interference with eosinophils was

 performed by intraperitoneal administration of anti-IL-5 (TRFK5), which

 neutralizes IL-5. Interference with neutrophils and neutrophil elastase

 was performed by intraperitoneal anti-Ly6G and sivelestat

 administration, respectively. Outcome parameters included eosinophils

 subsets (homeostatic EOS and inflammatory EOS), proinflammatory

 cytokines, goblet cell hyperplasia and airway

 hyperresponsiveness.ResultsThe administration of anti-IL-5 significantly

 decreased eosinophilic responses, affecting both inflammatory and

 homeostatic eosinophil subsets, upon subacute HDM + DEP exposure while

 BAL neutrophils, NET formation and other asthma features remained

 present. Neutrophils were significantly reduced after anti-Ly6G

 administration in BALF, lung and blood without affecting the

 eosinophilic inflammation upon HDM + DEP exposure. Sivelestat treatment

 tended to decrease BALF inflammation, including eosinophils, upon HDM +

 DEP exposure, but did not affect lung inflammation.ConclusionInhibition

 of IL-5 signalling, but not neutrophil interventions, significantly

 attenuates eosinophilic inflammation in a mouse model of mixed

 granulocytic asthma, elicited by air pollution exposure.}},
  articleno    = {{43}},
  author       = {{De Volder, Joyceline and Bontinck, Annelies and Haelterman, Valerie and Boon, Louis and Joos, Guy and Brusselle, Guy and Maes, Tania}},
  issn         = {{1465-993X}},
  journal      = {{RESPIRATORY RESEARCH}},
  keywords     = {{asthma,air pollution,inflammation}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{16}},
  title        = {{Anti-IL-5 treatment, but not neutrophil interference, attenuates inflammation in a mixed granulocytic asthma mouse model, elicited by air pollution}},
  url          = {{http://doi.org/10.1186/s12931-024-03082-9}},
  volume       = {{26}},
  year         = {{2025}},
}

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