Background/Purpose: TNF inhibitors are highly efficient in controlling disease activity and improving functional outcomes as well as quality of life in most ankylosing spondylitis patients; however, TNF inhibitors are not sufficiently effective for preventing the progression of consequent spinal damage. Recent clinical studies have shown that early control of disease by using TNF inhibitors prevents spinal damage. This study aimed to investigate the effect of early TNF inhibition on spinal inflammation in murine model of spondyloarthritis.

Methods: We injected curdlan in SKG mice at 8 weeks of age (curdlan group), and administered adalimumab (10 mg/kg) at 3 and 9 weeks after curdlan injection (ADA group). Clinical score of peripheral arthritis was evaluated, and serum cytokines were analyzed at 8 and 14 weeks after curdlan injection. T cell population in the spleen was measured by flow-cytometry. Spinal inflammation and cartilage destruction were evaluated by PET-MRI and histologic examination using H&E and toluidine blue staining. Opal multiplexed immunofluorescence staining for TNF-α, IL-17A, IL-22, and IL-23 was carried out in the spinal tissues at 16 weeks after curdlan injection.

Results: Clinical score of peripheral arthritis was decreased in the ADA group after 1 week of adalimumab injection. Serum levels of TNF-α, IL-17A, IL-22, IL-23, INF-gamma, and IL-6 at 8 weeks showed no significant difference between the two groups. According to splenocytes analysis, frequencies of CD4⁺ T cells, T_H17⁺ cells, and regulatory T cells were not significantly different between the two groups. However, H&E and toluene blue staining of curdlan group revealed severe inflammatory cell accumulation and intervertebral cartilage destruction in the spinal tissues. ¹⁸F-FDG uptake of thoracic spine level in paravertebral tissue was significantly lower in the ADA group. Also, the densities of TNF-α and IL-17A in immunofluorescent-stained paravertebral tissue were decreased in the ADA group, whereas the serum levels of these cytokines were not significantly different between the two groups at 14 weeks.

Conclusion: Curdlan-induced murine model of spondyloarthritis developed spinal inflammation and consequent cartilage destruction. Early introduction of TNF inhibitor prevented spinal inflammation and deformity in curdlan-induced spondyloarthritis mice via blocking TNF and IL-17A.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/early-injection-of-tnf-inhibitor-prevents-spinal-inflammation-and-deformity-in-curdlan-induced-spondyloarthritis-animal-model/