Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection
IntroductionSerum levels of interleukin-6 (IL-6) are increased in COVID-19 patients. IL-6 is an effective therapeutic target in inflammatory diseases and tocilizumab, a monoclonal antibody that blocks signaling via the IL-6 receptor (IL-6R), is used to treat patients with severe COVID-19. However, t...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1488745/full |
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| author | Juliane Lokau Juliane Lokau Yvonne Garbers Manuel M. Vicente Anna Dittrich Stefan Meltendorf Holger Lingel Anja K. Münster-Kühnel Monika Brunner-Weinzierl Christoph Garbers Christoph Garbers |
| author_facet | Juliane Lokau Juliane Lokau Yvonne Garbers Manuel M. Vicente Anna Dittrich Stefan Meltendorf Holger Lingel Anja K. Münster-Kühnel Monika Brunner-Weinzierl Christoph Garbers Christoph Garbers |
| author_sort | Juliane Lokau |
| collection | DOAJ |
| description | IntroductionSerum levels of interleukin-6 (IL-6) are increased in COVID-19 patients. IL-6 is an effective therapeutic target in inflammatory diseases and tocilizumab, a monoclonal antibody that blocks signaling via the IL-6 receptor (IL-6R), is used to treat patients with severe COVID-19. However, the IL-6R exists in membrane-bound and soluble forms (sIL-6R), and the sIL-6R in combination with soluble glycoprotein 130 (sgp130) forms an IL-6-neutralizing buffer system capable of neutralizing small amounts of IL-6.MethodsIn this study, we analyzed serum levels of IL-6, sIL-6R and sgp130 in the serum of COVID-19 convalescent individuals with a history of mild COVID-19 disease and in acute severely ill COVID-19 patients compared to uninfected control subjects. Furthermore, we used single cell RNA sequencing data in order to determine which immune cell types are sources and targets of the individual cytokines and whether their expression is altered in severe COVID-19 patients.ResultsWe find that sIL-6R levels are not only increased in acute severely ill patients, but also in convalescents after a mild COVID-19 infection. We show that this increase in sIL-6R results in an enhanced capacity of the sIL-6R/sgp130 buffer system, but that significantly enhanced free IL-6 is still present due to an overload of the buffer. Further, we identify IL-6 serum levels, age and the number of known pre-existing medical conditions as crucial determinants of disease outcome for the patients. We also show that IL-11 has no major systemic role in COVID-19 patients and that sCD25 is only increased in acute severely ill COVID-19 patients, but not in mild convalescent individuals.DiscussionIn conclusion, our study shows long-lasting alterations of the IL-6 system after COVID-19 disease, which might be relevant when applying anti-IL-6 or anti-IL-6R therapy. |
| format | Article |
| id | doaj-art-9475d6c2a29041999d6890f585171c88 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-9475d6c2a29041999d6890f585171c882025-01-06T06:59:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14887451488745Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infectionJuliane Lokau0Juliane Lokau1Yvonne Garbers2Manuel M. Vicente3Anna Dittrich4Stefan Meltendorf5Holger Lingel6Anja K. Münster-Kühnel7Monika Brunner-Weinzierl8Christoph Garbers9Christoph Garbers10Institute of Clinical Biochemistry, Hannover Medical School, Hannover, GermanyDepartment of Pathology, Otto-von-Guericke-University Magdeburg, Medical Faculty, Magdeburg, GermanyFaculty of Management, Culture and Technology (Lingen campus), Osnabrück University of Applied Sciences, Lingen, GermanyInstitute of Clinical Biochemistry, Hannover Medical School, Hannover, GermanyDepartment of Systems Biology, Institute of Biology, Otto-von-Guericke-University Magdeburg, Magdeburg, GermanyDepartment of Experimental Pediatrics, Otto-von-Guericke-University Magdeburg, Magdeburg, GermanyDepartment of Experimental Pediatrics, Otto-von-Guericke-University Magdeburg, Magdeburg, GermanyInstitute of Clinical Biochemistry, Hannover Medical School, Hannover, GermanyDepartment of Experimental Pediatrics, Otto-von-Guericke-University Magdeburg, Magdeburg, GermanyInstitute of Clinical Biochemistry, Hannover Medical School, Hannover, GermanyDepartment of Pathology, Otto-von-Guericke-University Magdeburg, Medical Faculty, Magdeburg, GermanyIntroductionSerum levels of interleukin-6 (IL-6) are increased in COVID-19 patients. IL-6 is an effective therapeutic target in inflammatory diseases and tocilizumab, a monoclonal antibody that blocks signaling via the IL-6 receptor (IL-6R), is used to treat patients with severe COVID-19. However, the IL-6R exists in membrane-bound and soluble forms (sIL-6R), and the sIL-6R in combination with soluble glycoprotein 130 (sgp130) forms an IL-6-neutralizing buffer system capable of neutralizing small amounts of IL-6.MethodsIn this study, we analyzed serum levels of IL-6, sIL-6R and sgp130 in the serum of COVID-19 convalescent individuals with a history of mild COVID-19 disease and in acute severely ill COVID-19 patients compared to uninfected control subjects. Furthermore, we used single cell RNA sequencing data in order to determine which immune cell types are sources and targets of the individual cytokines and whether their expression is altered in severe COVID-19 patients.ResultsWe find that sIL-6R levels are not only increased in acute severely ill patients, but also in convalescents after a mild COVID-19 infection. We show that this increase in sIL-6R results in an enhanced capacity of the sIL-6R/sgp130 buffer system, but that significantly enhanced free IL-6 is still present due to an overload of the buffer. Further, we identify IL-6 serum levels, age and the number of known pre-existing medical conditions as crucial determinants of disease outcome for the patients. We also show that IL-11 has no major systemic role in COVID-19 patients and that sCD25 is only increased in acute severely ill COVID-19 patients, but not in mild convalescent individuals.DiscussionIn conclusion, our study shows long-lasting alterations of the IL-6 system after COVID-19 disease, which might be relevant when applying anti-IL-6 or anti-IL-6R therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1488745/fullinterleukin-6interleukin-6 receptorgp130COVID-19sCD25 |
| spellingShingle | Juliane Lokau Juliane Lokau Yvonne Garbers Manuel M. Vicente Anna Dittrich Stefan Meltendorf Holger Lingel Anja K. Münster-Kühnel Monika Brunner-Weinzierl Christoph Garbers Christoph Garbers Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection Frontiers in Immunology interleukin-6 interleukin-6 receptor gp130 COVID-19 sCD25 |
| title | Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection |
| title_full | Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection |
| title_fullStr | Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection |
| title_full_unstemmed | Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection |
| title_short | Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection |
| title_sort | long term increase in soluble interleukin 6 receptor levels in convalescents after mild covid 19 infection |
| topic | interleukin-6 interleukin-6 receptor gp130 COVID-19 sCD25 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1488745/full |
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