Interleukins

Abstract

The interleukins are a major class of biologically active protein mediators, known as cytokines, that following release from activated cells bind to specific cell surface receptors to induce growth and differentiating functions in target cells. Extensive studies into their genes, structures, receptors, signal transduction pathways and activities in experimental cell cultures have provided considerable knowledge leading to their molecular and biological characterisation. Fundamental findings are that they are mostly pleiotropic mediators, that is, act on more than one cell type or at different stages of cellular development, and stimulate multiple activities, especially where acting in combinations of two or more interleukins. Their production as essentially pure recombinant proteins has enabled studies in experimental model systems to determine whether their activities could be of clinical benefit, or harmful. Subsequently, several interleukins and their antagonists have been evaluated for clinical efficacy and safety in clinical studies, and have yielded promising, though not fully effective, therapeutic treatments for patients with cancer and autoinflammatory diseases. In this article, the molecular characteristics of interleukins, their cognate receptors and intracellular signalling pathways, their biological activities and their potential clinical uses are briefly described. Key Concepts: Interleukins are a broad class of biologically active proteins with hormone‐like actions that regulate the development, differentiation and functions of cells of the immune and haematopoietic systems. The activities of interleukins are mediated via cell surface receptors. Binding of interleukins to receptors triggers gene induction via the activation of intracellular signal transduction pathways. Interleukins exhibit complex biological interactions, both among themselves and with other molecular mediators, in vivo . The proinflammatory and immune‐stimulatory activities of interleukins are essential for host defence against pathogens. Interleukins can be ‘two‐edged swords’, being largely beneficial to the host at low concentrations but deleterious and toxic at high concentrations. The biological properties of interleukins have suggested their potential for development as therapeutic drugs (biopharmaceuticals) against infections and chronic diseases, such as cancer, but so far only a few have proved clinically useful. Antibody and receptor antagonists of interleukins are showing promise for the treatment of autoinflammatory and autoimmune diseases, such as irritable bowel disorders and RA.

Insights on the role of cytokines in carious lesions

“…The type 2 immune response promotes B-cell activities, with IL-4 acting as the prototypic cytokine molecule and in association with IL-6 [59]. Therefore, action on Th 2 lymphocytes to secrete cytokines during pulpal inflammation leads to production and increased levels of IL-4 and IL-6, releasing the two pro-inflammatory cytokines within the diseased tissue [60].…”