[Advances in interleukin-6 therapy]

Abstract

Interleukin-6 (IL-6) exhibits multiple biologic activities such as regulation of immunological responses and hematopoiesis, promotion of acute inflammation, and stimulation of some malignant and non-malignant cell growth. The IL-6 receptor system consists of an IL-6 specific binding molecule, IL-6R and a signal transducer, gp130. Following gp130 dimerization, IL-6 activates multiple signaling pathways (Ras dependent MAPk cascade, STAT1-STAT3 heterodimer pathway, and STAT3 homodimer pathway). Several other cytokines including oncostatin M, IL-11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF) and cardiotropin-1 (CT-1) use gp130 as a common signal transducing molecule and therefore have similar biological activities. Two major in vivo functions of IL-6 are reported. Firstly, IL-6 acts as a growth factor of some malignant and non-malignant cells such as malignant plasma cells in multiple myeloma, mesangial cells in the kidney, and keratinocytes. Secondly, IL-6 mediates inflammatory and immune responses in rheumatoid arthritis, Castleman disease, psoriasis, cardiac myxoma, cachexia, and other inflammatory conditions. Recently, a humanized anti-IL-6 receptor antibody was developed. Neutralization of IL-6 activity by the humanized anti-IL-6 receptor antibody may be a new therapeutic approach for IL-6 related diseases such as multiple myeloma, Castleman disease and rheumatoid arthritis.