Specific targeting of IL-6 signalling pathway: a new way to treat IBD?

Abstract

These uncertainties are particularly illustrated by the case of interleukin (IL)-6. The in vivo functions of this cytokine remain debated, IL-6 being considered alternatively as a pro- or anti-inflammatory cytokine,1 ,2 or sometimes as a key factor to polarise Th2 cells.3 Moreover, the IL-6 signalling is particular involving a phenomenon calledtrans signalling.4 Briefly, the receptor for IL-6 consists of two subunits: a ligand binding component (IL-6R) and a signal-transducing glycoprotein 130 (gp130) which is a member of the cytokine receptor superfamily (including also IL-11 and the leukaemia inhibitory factor). A soluble form of the ligand specific chain (sIL-6R), when complexed to IL-6, is capable of binding to the membrane bound gp130 and thus can elicit a signal-transduction involving STAT-3.5 This phenomenon called trans signalling introduced a novel aspect of cytokine action (fig 1).