{"id":{"repo_id":"ghent","oai_identifier":"oai:archive.ugent.be:472347"},"canonical_url":"https://search.dev.ndltd.org/etd/ghent/oai:archive.ugent.be:472347","repository":{"repo_id":"ghent","name":"Ghent University","base_url":"https://biblio.ugent.be/oai"},"display":{"title":"EOSINOPHILIC INFLAMMATION IN NASAL POLYPOSIS: REGULATION OF INTERLEUKIN 5 AND INTERLEUKIN 5 RECEPTOR α ISOFORMS","abstract":"As the vast majority of bilateral nasal polyps (NP) are associated with a prominent eosinophilic inflammation and as eosinophils are well recognised in eliciting tissue damage and subsequent re-modelling, we aimed to investigate the role of eosinophils in the pathogenesis of NP. Especially the regulation of interleukin-5 (IL-5) and the interleukin-5 receptor α (Rα) isoforms were studied with emphasis on future therapeutic strategies in NP. Characterisation of NP suggests a central deposition of plasma proteins (albumin), regulated by the subepithelial, mainly eosinophilic inflammation, as pathogenetic principle of polyp formation and growth. The accumulation and activation of eosinophils is favoured by the low concentrations of TGF- β1 and overproduction of IL-5 and eotaxin in NP tissue. Although elevated IgE levels are found in NP, total IgE and IgE antibodies in NP tissue was unrelated to skin prick tests, but correlated with the degree of eosinophilia. In addition, we demonstrated the organisation of secondary lymphoid tissue in NP tissue and a polyclonal hyper-immunoglobulinemia E associated with the presence of IgE specific to S. aureus enterotoxins (SAEs), colonization with S. aureus, and increased eosinophilic inflammation in a relevant subgroup of NP patients. The ultimate way to test the role of IL-5 and eosinophils in the pathogenesis of nasal polyposis, is by antagonizing IL-5 in an interventional study in NP patients. However, eosinophils show varying IL-5 sensitivity due to a different expression of the IL-5R isoforms according to activation state, maturation and localization in the body. At the local tissue level, the membrane-anchored (TM) IL-5R isoform is down-regulated whereas the secreted (SOL) IL-5R variant is up-regulated in nasal polyp tissue, but eosinophils are still activated. Therefore, strategies to antagonize IL-5 may have to face unexpected difficulties. We demonstrated shrinkage of nasal polyps in half of the verum-treated patients for up to four weeks after intravenous injection of a single dose of an anti-human IL-5 monoclonal antibody. When carefully analysing responders and non-responders, only those nasal polyps with elevated baseline levels of IL-5 in nasal secretions seemed to benefit from anti-IL-5 treatment. Remarkably, the degree of eosinophilia at baseline was not different between responders and non-responders. Our data show that at least in 50% of the nasal polyps, IL-5 and eosinophils play a key role (IL-5-dependent) in sustaining polyp size, whereas in the other group, eosinophilia may be more dependent on other factors (IL-5-independent). Finally, these insights in the regulation of IL-5 and eosinophilia in NP, (re-)open therapeutic perspectives in nasal polyposis based on eosinophil-selective targets.","abstract_html":"As the vast majority of bilateral nasal polyps (NP) are associated with a prominent eosinophilic inflammation and as eosinophils are well recognised in eliciting tissue damage and subsequent re-modelling, we aimed to investigate the role of eosinophils in the pathogenesis of NP. Especially the regulation of interleukin-5 (IL-5) and the interleukin-5 receptor α (Rα) isoforms were studied with emphasis on future therapeutic strategies in NP. Characterisation of NP suggests a central deposition of plasma proteins (albumin), regulated by the subepithelial, mainly eosinophilic inflammation, as pathogenetic principle of polyp formation and growth. The accumulation and activation of eosinophils is favoured by the low concentrations of TGF- β1 and overproduction of IL-5 and eotaxin in NP tissue. Although elevated IgE levels are found in NP, total IgE and IgE antibodies in NP tissue was unrelated to skin prick tests, but correlated with the degree of eosinophilia. In addition, we demonstrated the organisation of secondary lymphoid tissue in NP tissue and a polyclonal hyper-immunoglobulinemia E associated with the presence of IgE specific to S. aureus enterotoxins (SAEs), colonization with S. aureus, and increased eosinophilic inflammation in a relevant subgroup of NP patients. The ultimate way to test the role of IL-5 and eosinophils in the pathogenesis of nasal polyposis, is by antagonizing IL-5 in an interventional study in NP patients. However, eosinophils show varying IL-5 sensitivity due to a different expression of the IL-5R isoforms according to activation state, maturation and localization in the body. At the local tissue level, the membrane-anchored (TM) IL-5R isoform is down-regulated whereas the secreted (SOL) IL-5R variant is up-regulated in nasal polyp tissue, but eosinophils are still activated. Therefore, strategies to antagonize IL-5 may have to face unexpected difficulties. We demonstrated shrinkage of nasal polyps in half of the verum-treated patients for up to four weeks after intravenous injection of a single dose of an anti-human IL-5 monoclonal antibody. When carefully analysing responders and non-responders, only those nasal polyps with elevated baseline levels of IL-5 in nasal secretions seemed to benefit from anti-IL-5 treatment. Remarkably, the degree of eosinophilia at baseline was not different between responders and non-responders. Our data show that at least in 50% of the nasal polyps, IL-5 and eosinophils play a key role (IL-5-dependent) in sustaining polyp size, whereas in the other group, eosinophilia may be more dependent on other factors (IL-5-independent). Finally, these insights in the regulation of IL-5 and eosinophilia in NP, (re-)open therapeutic perspectives in nasal polyposis based on eosinophil-selective targets.","abstract_has_math":false,"creators":["Gevaert, Philippe"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Van Cauwenberge, P","Bachert, C"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2004,"date_issued":"2004","date_published":"2004","updated_at":"2026-07-24T02:22:55Z","subjects":[],"languages":["und"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://biblio.ugent.be/publication/472347","http://doi.org/1854/5550","https://biblio.ugent.be/publication/472347/file/1875745"],"render_values":[{"text":"https://biblio.ugent.be/publication/472347","href":"https://biblio.ugent.be/publication/472347","code":true},{"text":"http://doi.org/1854/5550","href":"http://doi.org/1854/5550","code":true},{"text":"https://biblio.ugent.be/publication/472347/file/1875745","href":"https://biblio.ugent.be/publication/472347/file/1875745","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/1854/LU-472347","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Van Cauwenberge, P","Bachert, C"]},{"key":"dc:creator","label":"Author","values":["Gevaert, Philippe"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2004"]},{"key":"dc:type","label":"Dc Type","values":["dissertation","info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["und"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://biblio.ugent.be/publication/472347","http://hdl.handle.net/1854/LU-472347","http://doi.org/1854/5550","https://biblio.ugent.be/publication/472347/file/1875745"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["As the vast majority of bilateral nasal polyps (NP) are associated with a prominent eosinophilic inflammation and as eosinophils are well recognised in eliciting tissue damage and subsequent re-modelling, we aimed to investigate the role of eosinophils in the pathogenesis of NP. Especially the regulation of interleukin-5 (IL-5) and the interleukin-5 receptor α (Rα) isoforms were studied with emphasis on future therapeutic strategies in NP. Characterisation of NP suggests a central deposition of plasma proteins (albumin), regulated by the subepithelial, mainly eosinophilic inflammation, as pathogenetic principle of polyp formation and growth. The accumulation and activation of eosinophils is favoured by the low concentrations of TGF- β1 and overproduction of IL-5 and eotaxin in NP tissue. Although elevated IgE levels are found in NP, total IgE and IgE antibodies in NP tissue was unrelated to skin prick tests, but correlated with the degree of eosinophilia. In addition, we demonstrated the organisation of secondary lymphoid tissue in NP tissue and a polyclonal hyper-immunoglobulinemia E associated with the presence of IgE specific to S. aureus enterotoxins (SAEs), colonization with S. aureus, and increased eosinophilic inflammation in a relevant subgroup of NP patients. The ultimate way to test the role of IL-5 and eosinophils in the pathogenesis of nasal polyposis, is by antagonizing IL-5 in an interventional study in NP patients. However, eosinophils show varying IL-5 sensitivity due to a different expression of the IL-5R isoforms according to activation state, maturation and localization in the body. At the local tissue level, the membrane-anchored (TM) IL-5R isoform is down-regulated whereas the secreted (SOL) IL-5R variant is up-regulated in nasal polyp tissue, but eosinophils are still activated. Therefore, strategies to antagonize IL-5 may have to face unexpected difficulties. We demonstrated shrinkage of nasal polyps in half of the verum-treated patients for up to four weeks after intravenous injection of a single dose of an anti-human IL-5 monoclonal antibody. When carefully analysing responders and non-responders, only those nasal polyps with elevated baseline levels of IL-5 in nasal secretions seemed to benefit from anti-IL-5 treatment. Remarkably, the degree of eosinophilia at baseline was not different between responders and non-responders. Our data show that at least in 50% of the nasal polyps, IL-5 and eosinophils play a key role (IL-5-dependent) in sustaining polyp size, whereas in the other group, eosinophilia may be more dependent on other factors (IL-5-independent). Finally, these insights in the regulation of IL-5 and eosinophilia in NP, (re-)open therapeutic perspectives in nasal polyposis based on eosinophil-selective targets."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["EOSINOPHILIC INFLAMMATION IN NASAL POLYPOSIS: REGULATION OF INTERLEUKIN 5 AND INTERLEUKIN 5 RECEPTOR α ISOFORMS"]}]}],"canonical_facts":{"dc:contributor":["Van Cauwenberge, P","Bachert, C"],"dc:creator":["Gevaert, Philippe"],"dc:date":["2004"],"dc:description":["As the vast majority of bilateral nasal polyps (NP) are associated with a prominent eosinophilic inflammation and as eosinophils are well recognised in eliciting tissue damage and subsequent re-modelling, we aimed to investigate the role of eosinophils in the pathogenesis of NP. Especially the regulation of interleukin-5 (IL-5) and the interleukin-5 receptor α (Rα) isoforms were studied with emphasis on future therapeutic strategies in NP. Characterisation of NP suggests a central deposition of plasma proteins (albumin), regulated by the subepithelial, mainly eosinophilic inflammation, as pathogenetic principle of polyp formation and growth. The accumulation and activation of eosinophils is favoured by the low concentrations of TGF- β1 and overproduction of IL-5 and eotaxin in NP tissue. Although elevated IgE levels are found in NP, total IgE and IgE antibodies in NP tissue was unrelated to skin prick tests, but correlated with the degree of eosinophilia. In addition, we demonstrated the organisation of secondary lymphoid tissue in NP tissue and a polyclonal hyper-immunoglobulinemia E associated with the presence of IgE specific to S. aureus enterotoxins (SAEs), colonization with S. aureus, and increased eosinophilic inflammation in a relevant subgroup of NP patients. The ultimate way to test the role of IL-5 and eosinophils in the pathogenesis of nasal polyposis, is by antagonizing IL-5 in an interventional study in NP patients. However, eosinophils show varying IL-5 sensitivity due to a different expression of the IL-5R isoforms according to activation state, maturation and localization in the body. At the local tissue level, the membrane-anchored (TM) IL-5R isoform is down-regulated whereas the secreted (SOL) IL-5R variant is up-regulated in nasal polyp tissue, but eosinophils are still activated. Therefore, strategies to antagonize IL-5 may have to face unexpected difficulties. We demonstrated shrinkage of nasal polyps in half of the verum-treated patients for up to four weeks after intravenous injection of a single dose of an anti-human IL-5 monoclonal antibody. When carefully analysing responders and non-responders, only those nasal polyps with elevated baseline levels of IL-5 in nasal secretions seemed to benefit from anti-IL-5 treatment. Remarkably, the degree of eosinophilia at baseline was not different between responders and non-responders. Our data show that at least in 50% of the nasal polyps, IL-5 and eosinophils play a key role (IL-5-dependent) in sustaining polyp size, whereas in the other group, eosinophilia may be more dependent on other factors (IL-5-independent). Finally, these insights in the regulation of IL-5 and eosinophilia in NP, (re-)open therapeutic perspectives in nasal polyposis based on eosinophil-selective targets."],"dc:format":["application/pdf"],"dc:identifier":["https://biblio.ugent.be/publication/472347","http://hdl.handle.net/1854/LU-472347","http://doi.org/1854/5550","https://biblio.ugent.be/publication/472347/file/1875745"],"dc:language":["und"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:title":["EOSINOPHILIC INFLAMMATION IN NASAL POLYPOSIS: REGULATION OF INTERLEUKIN 5 AND INTERLEUKIN 5 RECEPTOR α ISOFORMS"],"dc:type":["dissertation","info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]},"updated_at":"2026-07-24T02:22:55Z"}