Pathogenesis of rheumatoid arthritis. Part III: cytokines and joint destruction

Cytokines, proteins secreted by various cell types, regulate innate and acquired immunity as well as cartilage and bone metabolism. In rheumatoid arthritis (RA), cytokines exerting proinflammatory and prodestructive effects are overproduced, stimulate synthesis of cartilage degrading enzymes, generation of bone-resorbing osteoclasts and some of them inhibit the development of bone-forming osteoblasts. Due to these activities, cytokines became the first targets of biological therapies applied in RA. However, neutralization of select cytokines has been revealed to restrain immune and inflammatory responses and to slow radiological progression in some patients only. Therefore, intensive researches aimed at new therapy development are in progress. The improvement of knowledge on cytokine biology and cartilage and bone homeostatic mechanisms allows many new molecules to be proposed as potential therapeutic targets, and numerous new biological drugs are tested in clinical trials. These topics are reviewed and a scheme illustrating destruction of joint cartilage and bone in RA is shown in the figure 1.