Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases

Abstract

Interleukin-1 (IL-1) is a master cytokine in the pathogenesis of several diseases, inducing multiple pathways of inflammation. Inflammation is part of every disease, acute or chronic. Diseases in which monocytes and/or macrophages and neutrophils have a dominant role are called autoinflammatory diseases. By contrast, diseases in which T lymphocytes have a major role are termed autoimmune diseases. Autoimmune diseases are treated with glucocorticoids, immunosuppressive drugs as well as various anti-cytokine-based therapeutics that target the immune system. Autoinflammatory diseases are uniquely responsive to IL-1-blocking therapies and are less responsive to immunosuppressors. There are two forms of IL-1: IL-1α and IL-1β. Both trigger inflammation by binding to the same receptor. The IL-1 receptor antagonist anakinra binds to the IL-1 receptor and blocks the activity of both IL-1α and IL-1β. A broad spectrum of acute and inflammatory diseases are treated with anakinra. Neutralizing monoclonal antibodies to IL-1α, IL-1β and the IL-1 receptor have been developed to decrease the activity of IL-1. An orally active inhibitor of caspase 1, the enzyme that processes IL-1β into an active cytokine, has also been developed. Blocking IL-1 in individuals with rare inherited diseases reverses generalized as well as local inflammation. Common inflammatory diseases such as arthritis, gout, type 2 diabetes, dry eye syndrome and heart failure are also responsive to IL-1 blocking. The future of IL-1 drug development will involve an expansion of disease indications through controlled trials.