Inhibition of IL-1β signaling by anakinra shows a critical role for bone loss in experimental arthritogenic alphavirus infections.

OBJECTIVE: Arthritogenic alphaviruses, such as Ross River virus (RRV), chikungunya virus (CHIKV), Sindbis virus (SINV), Barmah Forest virus, o'nyong-nyong virus and Mayaro virus cause sporadic and sometimes large outbreaks worldwide. These viruses particularly affect joints of the extremities and can lead to debilitating and potentially chronic polyarthritis/polyarthralgia. The host's innate immune response plays a crucial role in inducing pro-inflammatory host factors, leading to tissue destruction and bone loss in the joints. This study tested the effect of inhibiting IL-1 β signaling using the clinical RA drug anakinra on bone loss during arthritogenic alphavirus infections.

METHODS: Mice were infected with RRV or CHIKV and treated with anakinra. Weight gain and disease score was measured, tissue viral titers were determined, and histological changes in joint tissues were assessed.

RESULTS: Anakinra reduced RRV- and CHIKV-induced bone loss in the mouse model. In histological analysis of the knee joint, treatment with anakinra decreased epiphyseal growth plate thinning, the loss of epiphyseal bone volume and osteoclastogenesis in the tibia. Importantly, pharmacologic IL-1 receptor blockade did not enhance other clinical signs including disease score, weight loss or viremia.

CONCLUSION: The present experimental data suggest consideration of the further testing of anakinra for patients with arthritogenic alphavirus disease. This article is protected by copyright. All rights reserved.