Anti-cytokines and cytokines in the treatment of rheumatoid arthritis

The treatment approach to rheumatoid arthritis has undergone a major evolutionary change e in recent,Cars in part as a consequence of growing appreciation of the severity of this condition and in part due to very considerable progress in understanding the important role of cytokines in die immunopathogenesis of this disease. The major focus of this review is oil the rationale for targeting TNFalpha and IL-1 in rheumatoid arthritis and the results of clinical studies designed to assess the validity of this therapeutic approach. Recently published studies confirm that the long term use of a several biological agents targeting TNFalpha give rise to sustained improvements in symptoms and signs of rheumatoid disease and furthermore, that TNFalpha blockade protects joints from structural damage. Although these drugs are well tolerated and have a good over-all safety profile, pitfalls to the use of anti-TNFalpha agents apparent villi increasing clinical experience include rare cases of tuberculosis. The mechanism of action of anti-TNFalpha therapy is discussed. Clinical trials of interleukin-1 receptor antagonist show relatively modest anti-inflammatory eifficacy and an effect on X-ray indicative joint damage. Other pro-inflammatory cytokines representing potential therapeutic targets include of retardation of interferon-beta, interferon-gamma, IL6, IL-15, IL17 and IL-18. I will consider preliminary data, where available, arising from clinical trials designed to inhibit the activity Of such molecules. Ill this review I Will also discuss the rationale and preliminary data tor other potential therapeutic strategies designed to augment the activity of anti-inflammatory cytokines such as IL-4, IL-10, and IL-11 in rheumatoid disease.