Pharmacological role and clinical applications of interleukin-6 in rheumatoid disease

Abstract: Interleukin (IL)-6 is a pleiotropic cytokine that promotes polyclonal activation of association of the transducing glycoprotein 130 with the membrane-anchored receptor (R) α, IL-6 can generate functionally distinct signals. Given these particular molecular aspects, numerous activities ascribed to this cytokine are, in fact, due to the insertion into soluble IL-6Rα. The system is instrumental in rheumatoid arthritis (RA), Sjogren’s syndrome and systemic lupus erythema-tosus (SLE). In this respect, it is interesting that the expression of the recombination-activating gene is sustained by IL-6 in B lymphocytes, and repressed by anti-IL-6R antibody (Ab) in RA and SLE. Agents that inhibit IL-6 signaling have now entered clinical trials. As expected, clinical benefits are reported in the treatment of autoimmunedisorders with anti-IL-6R Ab, but other perspectives remain open in the forthcoming biotherapies of immune-mediated disorders. Keywords: interleukin-6, B lymphocyte, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, biotherapy