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Effect of tumor necrosis factor inhibition on spinal inflammation and spinal ankylosis in SKG mice
Doo-Ho Lim1, Eun-Ju Lee2, Oh Chan Kwon3
1Division of Rheumatology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
Abstract:
To prevent spinal progression in ankylosing spondylitis, initiating TNF-inhibitor treatment as early as possible is suggested. However, the outcomes are inconsistent in previous clinical studies. Here, we investigated the effect of TNF inhibition alone on spinal progression when used during arthritis development in a murine model. We injected 8-week-old SKG mice with curdlan (curdlan group). We injected adalimumab at 3 and 9 weeks after the first curdlan injection (ADA group). The clinical scores of peripheral arthritis decreased in the ADA group at 3 weeks after first adalimumab injection. Using positron emission tomography-magnetic resonance imaging and histologic examination, spinal inflammation was observed in the curdlan group, and was significantly deceased in the ADA group. However, spinal osteoblast activities by imaging using OsteoSense 680 EX and bone metabolism-related cytokines such as receptor activator of nuclear factor-kappa B ligand, osteoprotegerin, Dickkopf-1, and sclerostin levels except IL-17A level were not different between the two groups. We conclude that treating TNF inhibitor alone reduced peripheral arthritis score and spinal inflammation in curdlan-injected SKG mice but did not decrease the spinal osteoblast activity, suggesting little effect on spinal ankylosis.
Insights
Tumor necrosis factor (TNF) inhibitor treatment reduced peripheral arthritis and spinal inflammation in a mouse model of ankylosing spondylitis. However, it did not impact spinal bone metabolism, suggesting limited effects on spinal ankylosis.
Area of Science:
- Immunology
- Rheumatology
- Orthopedics
Background:
- Early TNF-inhibitor treatment is suggested for ankylosing spondylitis to prevent spinal progression.
- Clinical study outcomes regarding TNF inhibition for spinal progression are inconsistent.
- The specific effect of TNF inhibition alone on spinal progression during arthritis development needs further investigation.
Purpose of the Study:
- To investigate the effect of TNF inhibition alone on spinal progression in a murine model of arthritis.
- To assess whether adalimumab treatment impacts spinal inflammation and bone metabolism in curdlan-induced arthritis in SKG mice.
Main Methods:
- SKG mice were injected with curdlan to induce arthritis.
- Adalimumab (ADA) was administered at 3 and 9 weeks post-curdlan injection.
- Spinal inflammation and osteoblast activity were evaluated using PET-MRI, histology, and specific cytokine level analysis.
Main Results:
- Adalimumab treatment significantly decreased peripheral arthritis scores and spinal inflammation.
- No significant differences were observed in spinal osteoblast activity between the adalimumab and control groups.
- Levels of bone metabolism-related cytokines (except IL-17A) and osteoblast activity markers remained unchanged.
Conclusions:
- TNF inhibition alone effectively reduces peripheral arthritis and spinal inflammation in this model.
- TNF inhibition does not appear to significantly alter spinal osteoblast activity or bone metabolism.
- These findings suggest that TNF inhibitors alone may have limited efficacy in preventing spinal ankylosis in ankylosing spondylitis.
