The weight of interleukin-6 in B cell-related autoimmune disorders

Interleukin (IL)-6 is a prevailing factor of polyclonal B-cell activation of B cells, and thereby of their tolerance breach. Its receptor (R) complex consists of a transducing unit, and a membrane-bound or soluble protein. Many activities ascribed to this cytokine are generated by the soluble IL-6R. Evidence has however been gleaned in autoimmune diseases that the system is instrumental in rheumatoid arthritis (RA), Sjogren's syndrome and systemic lupus erythematosus (SLE). To gain insight into the understanding of the mechanisms behind these observations, a prime example is the recombination-activating gene (Rag) machinery in B lymphocytes. It is interesting that the expression of Rags is favored by IL-6, and repressed by anti-IL-6R antibody (Ab) in RA and SLE. Not surprisingly. clinical benefits are reported in the treatment of autoimmune disorders with anti-IL-6R Ab, and other perspectives about to be open in biotherapy. (C) 2009 Published by Elsevier Ltd.