IL4-10 Fusion Protein Shows DMOAD Activity in a Rat Osteoarthritis Model.
Cartilage
; 13(2_suppl): 1155S-1164S, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34159843
ABSTRACT
OBJECTIVE:
Ideally, disease-modifying osteoarthritis (OA) drugs (DMOAD) should combine chondroprotective, anti-inflammatory, and analgesic effects in a single molecule. A fusion protein of interleukin-4 (IL-4) and IL-10 (IL4-10 FP) possesses these combined effects. In this study, the DMOAD activity of rat IL4-10 FP (rIL4-10 FP) was tested in a rat model of surgically induced OA under metabolic dysregulation.DESIGN:
rIL4-10 FP was produced with HEK293F cells. Bioactivity of purified rIL4-10 FP was determined in a whole blood assay. Male Wistar rats (n = 20) were fed a high-fat diet (HFD) to induce metabolic dysregulation. After 12 weeks, OA was induced according to the Groove model. Two weeks after OA induction, rats were randomly divided into 2 groups and treated with 10 weekly, intra-articular injections of either rIL4-10 FP (n = 10) or phosphate buffered saline (PBS; n = 10). Possible antibody formation was evaluated using ELISA, cartilage degeneration and synovial inflammation were evaluated by histology and mechanical allodynia was evaluated using the von Frey test.RESULTS:
Intra-articular injections with rIL4-10 FP significantly reduced cartilage degeneration (P = 0.042) and decreased mechanical allodynia (P < 0.001) compared with PBS. Only mild synovial inflammation was found (nonsignificant), limiting detection of putative anti-inflammatory effects. Multiple injections of rIL4-10 FP did not induce antibodies against rIL4-10 FP.CONCLUSION:
rIL4-10 FP showed chondroprotective and analgesic activity in a rat OA model with moderate cartilage damage, mild synovial inflammation, and pain. Future studies will need to address whether less frequent intra-articular injections, for example, with formulations with increased residence time, would also lead to DMOAD activity.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
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Proteínas Recombinantes de Fusão
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Cartilagem Articular
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Interleucina-4
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Interleucina-10
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cartilage
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Holanda