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Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients

Osteoarthritis (OA) is the leading degenerative joint disease in the western world and leads, if left untreated, to a progressive deterioration of joint functionality, ultimately reducing quality of life. Recent data has shown, that especially OA of the ankle and foot are among the most frequently a...

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Autores principales: Weissmann, Thomas, Rückert, Michael, Zhou, Jian-Guo, Seeling, Michaela, Lettmaier, Sebastian, Donaubauer, Anna-Jasmina, Nimmerjahn, Falk, Ott, Oliver J., Hecht, Markus, Putz, Florian, Fietkau, Rainer, Frey, Benjamin, Gaipl, Udo S., Deloch, Lisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763318/
https://www.ncbi.nlm.nih.gov/pubmed/35046940
http://dx.doi.org/10.3389/fimmu.2021.777792
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author Weissmann, Thomas
Rückert, Michael
Zhou, Jian-Guo
Seeling, Michaela
Lettmaier, Sebastian
Donaubauer, Anna-Jasmina
Nimmerjahn, Falk
Ott, Oliver J.
Hecht, Markus
Putz, Florian
Fietkau, Rainer
Frey, Benjamin
Gaipl, Udo S.
Deloch, Lisa
author_facet Weissmann, Thomas
Rückert, Michael
Zhou, Jian-Guo
Seeling, Michaela
Lettmaier, Sebastian
Donaubauer, Anna-Jasmina
Nimmerjahn, Falk
Ott, Oliver J.
Hecht, Markus
Putz, Florian
Fietkau, Rainer
Frey, Benjamin
Gaipl, Udo S.
Deloch, Lisa
author_sort Weissmann, Thomas
collection PubMed
description Osteoarthritis (OA) is the leading degenerative joint disease in the western world and leads, if left untreated, to a progressive deterioration of joint functionality, ultimately reducing quality of life. Recent data has shown, that especially OA of the ankle and foot are among the most frequently affected regions. Current research in OA points towards a complex involvement of various cell and tissue types, often accompanied by inflammation. Low-dose radiotherapy (LDRT) is widely used for the treatment of degenerative and inflammatory diseases. While the reported analgesic effects are well known, the underlying molecular mechanisms are only poorly understood. We therefore correlated a clinical approach, looking at pain reduction in 196 patients treated with LDRT with a pre-clinical approach, utilizing the K/BxN serum transfer mouse model using flow cytometry and multiplex ELISA for analysis. While an improvement of symptoms in the majority of patients was found, patients suffering from symptoms within the tarsi transversa show a significantly lower level of improvement. Further, a significant impact of therapy success was detected depending on whether only one or both feet were affected. Further, patients of younger age showed a significantly better outcome than older ones while needing fewer treatment series. When looking on a cellular level within the mouse model, a systemic alteration of immune cells namely a shift from CD8+ to CD4+ T cells and reduced numbers of DCs was observed. A general reduction of inflammatory cytokines was detected, with significant alterations in IL-4 and IL-17 levels, all of which could potentially be responsible for the highly effective clinical improvement in patients. Taken together our data indicate that LDRT can be regarded as a highly effective treatment option for patients suffering from OA of the foot and ankle, in terms of analgesic effects, especially in younger patients. Furthermore, the observed effects are mediated by an interplay of cellular and soluble immune factors, as observed in the K/BxN serum transfer model. With this interdisciplinary approach we aim to encourage the usage of LDRT as an additive treatment strategy not only as a last resort, but also earlier in the course of disease.
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spelling pubmed-87633182022-01-18 Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients Weissmann, Thomas Rückert, Michael Zhou, Jian-Guo Seeling, Michaela Lettmaier, Sebastian Donaubauer, Anna-Jasmina Nimmerjahn, Falk Ott, Oliver J. Hecht, Markus Putz, Florian Fietkau, Rainer Frey, Benjamin Gaipl, Udo S. Deloch, Lisa Front Immunol Immunology Osteoarthritis (OA) is the leading degenerative joint disease in the western world and leads, if left untreated, to a progressive deterioration of joint functionality, ultimately reducing quality of life. Recent data has shown, that especially OA of the ankle and foot are among the most frequently affected regions. Current research in OA points towards a complex involvement of various cell and tissue types, often accompanied by inflammation. Low-dose radiotherapy (LDRT) is widely used for the treatment of degenerative and inflammatory diseases. While the reported analgesic effects are well known, the underlying molecular mechanisms are only poorly understood. We therefore correlated a clinical approach, looking at pain reduction in 196 patients treated with LDRT with a pre-clinical approach, utilizing the K/BxN serum transfer mouse model using flow cytometry and multiplex ELISA for analysis. While an improvement of symptoms in the majority of patients was found, patients suffering from symptoms within the tarsi transversa show a significantly lower level of improvement. Further, a significant impact of therapy success was detected depending on whether only one or both feet were affected. Further, patients of younger age showed a significantly better outcome than older ones while needing fewer treatment series. When looking on a cellular level within the mouse model, a systemic alteration of immune cells namely a shift from CD8+ to CD4+ T cells and reduced numbers of DCs was observed. A general reduction of inflammatory cytokines was detected, with significant alterations in IL-4 and IL-17 levels, all of which could potentially be responsible for the highly effective clinical improvement in patients. Taken together our data indicate that LDRT can be regarded as a highly effective treatment option for patients suffering from OA of the foot and ankle, in terms of analgesic effects, especially in younger patients. Furthermore, the observed effects are mediated by an interplay of cellular and soluble immune factors, as observed in the K/BxN serum transfer model. With this interdisciplinary approach we aim to encourage the usage of LDRT as an additive treatment strategy not only as a last resort, but also earlier in the course of disease. Frontiers Media S.A. 2022-01-03 /pmc/articles/PMC8763318/ /pubmed/35046940 http://dx.doi.org/10.3389/fimmu.2021.777792 Text en Copyright © 2022 Weissmann, Rückert, Zhou, Seeling, Lettmaier, Donaubauer, Nimmerjahn, Ott, Hecht, Putz, Fietkau, Frey, Gaipl and Deloch https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Weissmann, Thomas
Rückert, Michael
Zhou, Jian-Guo
Seeling, Michaela
Lettmaier, Sebastian
Donaubauer, Anna-Jasmina
Nimmerjahn, Falk
Ott, Oliver J.
Hecht, Markus
Putz, Florian
Fietkau, Rainer
Frey, Benjamin
Gaipl, Udo S.
Deloch, Lisa
Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients
title Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients
title_full Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients
title_fullStr Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients
title_full_unstemmed Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients
title_short Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients
title_sort low-dose radiotherapy leads to a systemic anti-inflammatory shift in the pre-clinical k/bxn serum transfer model and reduces osteoarthritic pain in patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763318/
https://www.ncbi.nlm.nih.gov/pubmed/35046940
http://dx.doi.org/10.3389/fimmu.2021.777792
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