Inhibition of Interleukin‐1β Signaling by Anakinra Demonstrates a Critical Role of Bone Loss in Experimental Arthritogenic Alphavirus Infections
| Autor: | Joseph R Freitas, Shambhavi Rao, Richard Bucala, Mark R. Forwood, Ali Zaid, Andreas Suhrbier, Adam Taylor, Suresh Mahalingam, Stefan Wolf, Lara J. Herrero |
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| Rok vydání: | 2019 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Knee Joint viruses Interleukin-1beta Immunology Arthritis Viremia Bone and Bones Virus Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Rheumatology Osteogenesis Ross River virus medicine Animals Immunology and Allergy Growth Plate 030212 general & internal medicine Alphavirus infection Arthritis Infectious Anakinra Tibia Alphavirus Infections business.industry virus diseases medicine.disease Interleukin 1 Receptor Antagonist Protein 030104 developmental biology Antirheumatic Agents Rheumatoid arthritis Chikungunya Fever Polyarthritis business Chikungunya virus medicine.drug |
| Zdroj: | Arthritis & Rheumatology. 71:1185-1190 |
| ISSN: | 2326-5205 2326-5191 |
| DOI: | 10.1002/art.40856 |
| Popis: | Objective: Arthritogenic alphaviruses, such as Ross River virus (RRV) and chikungunya virus (CHIKV), particularly affect joints of the extremities and can lead to debilitating and potentially chronic polyarthritis/polyarthralgia. The innate immune response of the host plays a crucial role in inducing proinflammatory host factors, leading to tissue destruction and bone loss in the joints. This study was performed to assess how the inhibition of interleukin-1β (IL-1β) signaling using the clinical rheumatoid arthritis drug anakinra influences bone loss in mice with arthritogenic alphavirus infections. Methods: Mice (n = 5 per group) were infected with RRV or CHIKV and then treated with anakinra. Weight gain and disease severity were measured, tissue viral titers were determined, and histologic changes in joint tissues were assessed. Results: Anakinra therapy reduced RRV- and CHIKV-induced bone loss in this murine model (P < 0.001 and P < 0.05, respectively). Histologic analysis of the knee joint showed that treatment with anakinra decreased epiphyseal growth plate thinning, loss of epiphyseal bone volume, and osteoclastogenesis in the tibia. Importantly, pharmacologic IL-1 receptor (IL-1R) blockade did not improve other clinical features, including disease score, weight loss, or viremia. Conclusion: The present findings suggest that anakinra therapy may reduce bone loss in experimental murine models of RRV and CHIKV. Further investigations are needed to assess the potential therapeutic benefits of anakinra in patients with arthritogenic alphavirus disease. |
| Databáze: | OpenAIRE |
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