Rheumatoid arthritis (RA) is a chronic systemic disease characterized by inflammation and multiplication of inflammation causing cells within the lining of the joints. This leads to progressive damage and bone destruction. In addition, because it is systemic disease, the same type of inflammatory changes are seen in other organ systems of the body.

It is the consensus of most researchers that RA is driven by chemical messengers called cytokines. These cytokines activate immune cells to attack the synovial lining of the joint. Among the most important cytokines are tumor necrosis- α (TNF) and interleukin -1β (IL-1).

These two cytokines have been the prime targets for the development of different therapies for RA. Drugs like Enbrel, Humira, and Remicade block the effects of TNF while Kineret blocks the effects of IL-1.

Another interesting cytokine that seems to play a significant role is interleukin-6. Studies have demonstrated that the fluid obtained from the inflamed joints of patients with RA have an increased level of IL-6. The increase in IL-6 correlates with laboratory signs of inflammation such as elevated erythrocyte sedimentation rate (ESR) as well as with clinical signs such as fever and anemia.

IL-6 is made by a number of different cells that are involved in the immune response. These include, among others, T cells and B cells. T cells and B cells are lymphocytes, a type of white blood cell, that is responsible for many immune functions. Another major source of IL-6 in RA is the synovial cell fibroblast, a type of cell that is found in the lining of the joint of patients with RA.

In laboratory experiments, it appears that IL-6 is necessary for the production of antibodies by B cells. IL-6 also activates T-cells, ie. makes them more likely to participate in the immune response.

A number of studies have shown that IL-6 is a major player in causing and perpetuating inflammation. What seems to be the primary process within the joint is the production of IL-6 by synovial fibroblasts (SF). The IL-6 then causes more SF to grow. Thus a cycle of SF growth leading to more IL-6, leading to more SF growth takes place.

Il-6 may also cause another type of cell, the osteoclast, to multiply. Osteoclasts chew away bone. This chewing away of bone leads to erosions, the hallmark of RA within the joint.

Because IL-6 has such a large role in destructive inflammation, it has been an attractive target for drug development.

Attempts to create an antibody against IL-6 have been successful. Tociluzamab is a humanized mouse antibody directed against human IL-6. Experiments have clearly shown that this product binds to and inhibits the inflammatory capability of IL-6. The tradename of tociluzamab is Actemra.

Clinical trials are ongoing investigating the safety, tolerability, and efficacy of this new compound.