Tumour necrosis factor and other proinflammatory cytokines in systemic lupus erythematosus: a rationale for therapeutic intervention.

Systemic lupus erythematosus (SLE) is an autoantibody and immune complex mediated disease. However, it is the ensuing inflammatory process that leads to irreversible organ damage. In fact several murine models of SLE suggest that this inflammatory organ damage can be prevented even in the presence of autoantibodies. Given data from experimental models as well as from patients, proinflammatory cytokines including tumour necrosis factor (TNF) alpha apparently play a significant role in the inflammatory process, but may have immunoregulatory functions at the same time. Therefore, anti-TNF alpha therapy may constitute an interesting candidate approach for treating SLE inflammatory organ disease, but potentially at the cost of increased autoantibody formation. Clinical trials will be required to answer whether TNF alpha blockade fulfils this hope with an acceptable safety profile. Interferon (IFN)-gamma, interleukin (IL)-18, IL-6 and possibly IL-1 are increased in SLE and likewise involved in the inflammatory process. Specific therapeutic agents for blocking these cytokines should be available in the near future.