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

Pierre Youinou^1,2, Sophie Hillion^1,2, Gabriel J Tobón^1,2, Divi Cornec^1,2, Jacques-Olivier Pers^1,2, Alain Saraux^1,2, Boutahar Bendaoud^1,2, Yves Renaudineau^1,2, Christophe Jamin^1,2

¹Université Européenne de Bretagne and Université de Brest, “Immunology and Pathology”, ²ScInBioS, Brest, France; University Medical School Hospital, Brest, France

Abstract: Interleukin (IL)-6 is a pleiotropic cytokine that promotes polyclonal activation of B lymphocytes. This implies that its deregulation favors inflammatory conditions. Through the 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), Sjögren’s syndrome and systemic lupus erythematosus (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 autoimmune disorders 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, Sjögren’s syndrome, biotherapy