UC San Diego

Rheumatoid arthritis (RA) is a chronic inflammatory disease involving synovial inflammation, autoantibody production and cartilage and bone destruction. It’s a progressive disease that if left untreated can cause irreversible damage. Current treatments have numerous mechanisms of action, deleterious side effects and are not always effective as monotherapies. Rheumatoid arthritis is a consequence of self-reactivity; however, it’s cause is not fully understood. Non-specific targeting of immunosuppressants can leave RA patients at risk for other diseases and infections. To better understand the molecular pathway involved in pain-like behavior and inflammation characteristic of this disease, the experiments performed focused on the innate immune system, specifically type I interferons, in a K/BxN-induced arthritis mouse model. It was found that interferon receptors expressed by microglia may be involved in the onset and persistence of allodynia. Several other interferon pathways studied had only slight attenuation or no impact on allodynia. Previous studies identified a compound, R-INH#5, that had immunosuppressant characteristics and attenuated allodynia in K/BxN arthritis potentially by inhibiting STING, a predominant type I interferon pathway. It was confirmed the compound significantly inhibited cytokine production and attenuated allodynia in a K/BxN arthritic mouse; however, the attenuation was transient and only observed if administered at the onset of arthritis.