Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still’s Disease and Active Articular Manifestation Responding to Canakinumab
Adult-onset Still’s disease (AOSD) is a systemic auto-inflammatory disease characterized by the presence of immunologically mediated inflammation and deficient resolution of inflammation. Canakinumab is an approved IL-1β inhibitor in the treatment of AOSD with a balanced efficacy and safety profile....
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/19/4400 |
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| author | Khetam Ghannam Jan Zernicke Claudia Kedor Joachim Listing Gerd-R. Burmester Dirk Foell Eugen Feist |
| author_facet | Khetam Ghannam Jan Zernicke Claudia Kedor Joachim Listing Gerd-R. Burmester Dirk Foell Eugen Feist |
| author_sort | Khetam Ghannam |
| collection | DOAJ |
| description | Adult-onset Still’s disease (AOSD) is a systemic auto-inflammatory disease characterized by the presence of immunologically mediated inflammation and deficient resolution of inflammation. Canakinumab is an approved IL-1β inhibitor in the treatment of AOSD with a balanced efficacy and safety profile. Since inflammatory cytokines play a major role in the pathogenesis of AOSD, we investigated the effects of canakinumab on the cytokine profile of AOSD patients from a randomized controlled trial. Multiplex analysis and ELISA were used to test the concentrations of several cytokines at three time points—week 0 (baseline), week 1 and week 4—in two patient groups—placebo and canakinumab. Two-way repeated-measures analysis of variance revealed a significant temporal effect on the concentrations of MRP 8/14, S100A12, IL-6 and IL-18 with a significant decrease at week 4 in the canakinumab group exclusively. Comparing responders with non-responders to canakinumab showed a significant decrease in MRP 8/14, IL-1RA, IL-18 and IL-6 in responders at week 4, while S100A12 levels decreased significantly in responders and non-responders. In summary, canakinumab showed a striking effect on the cytokine profile in patients with AOSD, exhibiting a clear association with clinical response. |
| first_indexed | 2024-03-10T06:57:58Z |
| format | Article |
| id | doaj.art-6cc4a71d05e74082a453fa8e13a738c1 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T06:57:58Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-6cc4a71d05e74082a453fa8e13a738c12023-11-22T16:18:53ZengMDPI AGJournal of Clinical Medicine2077-03832021-09-011019440010.3390/jcm10194400Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still’s Disease and Active Articular Manifestation Responding to CanakinumabKhetam Ghannam0Jan Zernicke1Claudia Kedor2Joachim Listing3Gerd-R. Burmester4Dirk Foell5Eugen Feist6Department of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, 10117 Berlin, GermanyEpidemiology Unit, German Rheumatism Research Centre, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, 10117 Berlin, GermanyPediatric Rheumatology and Immunology, University Hospital Muenster, 48149 Muenster, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, 10117 Berlin, GermanyAdult-onset Still’s disease (AOSD) is a systemic auto-inflammatory disease characterized by the presence of immunologically mediated inflammation and deficient resolution of inflammation. Canakinumab is an approved IL-1β inhibitor in the treatment of AOSD with a balanced efficacy and safety profile. Since inflammatory cytokines play a major role in the pathogenesis of AOSD, we investigated the effects of canakinumab on the cytokine profile of AOSD patients from a randomized controlled trial. Multiplex analysis and ELISA were used to test the concentrations of several cytokines at three time points—week 0 (baseline), week 1 and week 4—in two patient groups—placebo and canakinumab. Two-way repeated-measures analysis of variance revealed a significant temporal effect on the concentrations of MRP 8/14, S100A12, IL-6 and IL-18 with a significant decrease at week 4 in the canakinumab group exclusively. Comparing responders with non-responders to canakinumab showed a significant decrease in MRP 8/14, IL-1RA, IL-18 and IL-6 in responders at week 4, while S100A12 levels decreased significantly in responders and non-responders. In summary, canakinumab showed a striking effect on the cytokine profile in patients with AOSD, exhibiting a clear association with clinical response.https://www.mdpi.com/2077-0383/10/19/4400adult-onset Still’s diseasecanakinumabcytokines |
| spellingShingle | Khetam Ghannam Jan Zernicke Claudia Kedor Joachim Listing Gerd-R. Burmester Dirk Foell Eugen Feist Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still’s Disease and Active Articular Manifestation Responding to Canakinumab Journal of Clinical Medicine adult-onset Still’s disease canakinumab cytokines |
| title | Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still’s Disease and Active Articular Manifestation Responding to Canakinumab |
| title_full | Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still’s Disease and Active Articular Manifestation Responding to Canakinumab |
| title_fullStr | Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still’s Disease and Active Articular Manifestation Responding to Canakinumab |
| title_full_unstemmed | Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still’s Disease and Active Articular Manifestation Responding to Canakinumab |
| title_short | Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still’s Disease and Active Articular Manifestation Responding to Canakinumab |
| title_sort | distinct effects of interleukin 1β inhibition upon cytokine profile in patients with adult onset still s disease and active articular manifestation responding to canakinumab |
| topic | adult-onset Still’s disease canakinumab cytokines |
| url | https://www.mdpi.com/2077-0383/10/19/4400 |
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