Remdesivir alleviates joint damage in collagen-induced arthritis and inhibits inflammatory cell death of RA synovial fibroblasts.

BACKGROUND

The antiviral agent, remdesivir, is adenosine analogue which is currently also used as anti-coronavirus disease 2019. Remdesivir also had anti-inflammatory effect which reduced pro-inflammatory cytokine production, and inhibition of the cyclic GMP-AMP synthase-STING pathway.

METHODS

We evaluated the antiarthritic effects of remdesivir in a mouse model of High-fat diet (HFD) collagen-induced arthritis (CIA) and in fibroblast-like synoviocytes from patients with RA. Type II collagen was administered to DBA/1J mice to induce CIA. Vehicle or remdesivir was injected subcutaneously three times a week. During 7 weeks of treatment, the arthritis score and incidence were evaluated twice a week. Flow cytometry and confocal imaging were used to evaluate CD4 + T cells in the spleen. FLSs from patients with RA were stimulated in vitro with remdesivir and tumor necrosis factor (TNF)-α, and western blotting was used to measure the expression of STING and necroptosis-related markers.

RESULTS

Remdesivir administration suppressed the incidence and progression of arthritis in mice with CIA. Histological analysis revealed lower inflammation and cartilage damage scores in remdesivir-treated than in vehicle groups. Interleukin (IL)-17 + CD4 + T-cell differentiation was inhibited in the remdesivir-treated group. Furthermore, IL-17/-6/-1β, monocyte chemoattractant protein -1, and TNF-α expression was reduced in the remdesivir group. In vitro, remdesivir suppressed the expression of STING, nuclear factor-κB, RIPK3, and phosphorylated MLKL in RA-FLSs under TNF-α stimulation.

CONCLUSIONS

The antiviral agent remdesivir suppressed arthritis by regulating Th cell differentiation, pro-inflammatory cytokine expression, the STING pathway, and necroptosis.