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Microbubble-enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced antiinflammatory effects in the knees of rabbits with antigen-induced arthritis
- Source :
- Arthritis & Rheumatism. 52:2559-2566
- Publication Year :
- 2005
- Publisher :
- Wiley, 2005.
-
Abstract
- Objective To evaluate whether microbubble-enhanced ultrasound (US) treatment promotes the delivery of methotrexate (MTX) into synovial cells and the enhanced antiinflammatory effects of intraarticular MTX therapy in a rabbit arthritis model. Methods Arthritis was induced in both knees of 53 rabbits by immunization with ovalbumin. MTX including a microbubble agent was then injected into the left and right knee joints, and the right knees were exposed to US (MTX+/US+ group), while the left knees were not (MTX+/US− group). The knee joints were evaluated histologically in 7 rabbits at 5 time points up to day 56. Quantitative gene expression of interleukin-1β (IL-1β) in synovial tissue was measured on days 7 and 28. Eight rabbits were used for the measurement of MTX concentration in synovial tissue 12 hours after treatment. To evaluate the effect of microbubble-enhanced US treatment in the absence of MTX, only the microbubble agent was injected into the left and right knee joints of 10 rabbits with or without US exposure, and these animals were evaluated histologically on days 7 and 28. Results The MTX concentration in synovial tissue was significantly higher in the MTX+/US+ group than in the MTX+/US− group. Synovial inflammation was less prominent in the MTX+/US+ group compared with the MTX+/US− group, judging from the results of the histologic evaluation and the gene expression levels of IL-1β in synovial tissue. It also appeared that microbubble-enhanced US exposure itself did not affect inflammation. Conclusion Microbubble-enhanced US exposure promoted the uptake of MTX into synovial cells, which resulted in enhancement of the antiinflammatory effects of the intraarticular MTX injection. These results suggest that application of this technique may have clinical benefit.
- Subjects :
- musculoskeletal diseases
Pathology
medicine.medical_specialty
Knee Joint
Ovalbumin
medicine.drug_class
Immunology
Anti-Inflammatory Agents
Arthritis
Inflammation
Antimetabolite
Injections, Intra-Articular
chemistry.chemical_compound
Rheumatology
immune system diseases
medicine
Animals
Immunology and Allergy
Ultrasonics
heterocyclic compounds
Pharmacology (medical)
skin and connective tissue diseases
Microbubbles
Lagomorpha
biology
business.industry
Osmolar Concentration
Synovial Membrane
biology.organism_classification
medicine.disease
Arthritis, Experimental
Methotrexate
chemistry
Synovial Cell
Antifolate
biology.protein
Rabbits
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 15290131 and 00043591
- Volume :
- 52
- Database :
- OpenAIRE
- Journal :
- Arthritis & Rheumatism
- Accession number :
- edsair.doi.dedup.....27a50ecfdba52acd59aa71aacfb0788f