Rheumatoid arthritis is a chronic, destructive inflammation, primarily of the joints, that affects up to 1% of the world's population. The cause of the disease is not known, but its progression is autoimmune: immune cells called macrophages, which normally die after attacking an invader, instead persist and collect in the cartilage and bone, where their proliferation results in inflammation and joint destruction. The proliferation is thought to stem from an imbalance or deficiency in the signaling pathways for apoptosis (programmed cell death). Currently available treatments for rheumatoid arthritis include chemotherapy and steroid administration, but these are not effective in all patients and may have unwanted side effects.

Now, Harris Perlman (Northwestern University, Feinberg School of Medicine, Chicago, IL) and colleagues report that expression of Bim, a pro-apoptotic protein, is deficient in joints affected by rheumatoid arthritis and that treatment with a molecule similar to Bim protected mice against rheumatoid arthritis and even reversed the disease course in mice that had already developed rheumatoid arthritis.

The researchers first examined expression of Bim in the synovial lining of joints of people with rheumatoid arthritis. Bim expression was decreased in macrophages in these tissues, and the decrease in Bim expression was associated with an increase in inflammatory score. They found that Bim controlled the activation of macrophages and that decreased Bim expression contributed to increased macrophage activation.

Because the proliferation of macrophages contributes to the development of rheumatoid arthritis and Bim expression seems to limit macrophage proliferation, Perlman's group decided to test whether a peptide that mimics the expression of Bim (a mimetic) could interfere with the development of rheumatoid arthritis. They induced an early stage of inflammatory arthritis in mice and then treated some of them with the mimetic. Treatment with the mimetic reduced ankle circumference (an indicator of inflammation associated with arthritis), arthritis development, bone erosion and inflammation in the mice (Arthritis Rheum. 62, 441–451; 2010). They also tested the mimetic in mice with established inflammatory arthritis and found that it reduced ankle circumference and bone erosion in these mice as well. Notably, the mimetic was nontoxic and did not affect kidney or liver function in the mice.

The study results suggest that the Bim mimetic may have therapeutic potential for rheumatoid arthritis in humans. Further studies are needed to evaluate the treatment in other models of inflammatory arthritis and to develop a more precise technique for administering the mimetic.