Treatment of Inflammatory Diseases with IL-1 Blockade.

ABSTRACT: Background:Autoinflammatory diseases are distinct from autoimmune diseases. Whereas autoinflammatory diseases are due to dysfunctional T-cells and B-cells, autoinflammatory diseases are due to overproduction of macrophage cytokines particularly interleukin-1 beta (IL-1?). A causative role for IL-1 in autoinflammatory diseases is derived from clinical studies blocking the IL-1 receptor or neutralizing monoclonal antibodies or soluble receptors. Methods:A review was performed of clinical trials in autoinflammatory diseases using the IL-1 receptor antagonist (anakinra), the soluble IL-1 receptor (rilonacept), antibodies to IL-1? (canakinumab, gevokizumab) and anti-IL-1? (xilonix). Findings:Anakinra blocks the IL-1 Receptor type 1 (IL-1R1) and therefore blocks the activities of both IL-1? and IL-1?. Off-label use of anakinra is common for a broad spectrum of inflammatory diseases. Neutralization of IL-1? is used to treat hereditary autoinflammatory diseases but also atherosclerosis. Rilonacept reduces arterial wall inflammation in patients with chronic kidney disease. Neutralization of IL-1? has prolonged life in patients with advanced metastatic colorectal cancer. Compared to other cytokine blocking therapies, reducing the activities of IL-1 has an excellent safety record. Conclusions:Blocking IL-1 therapies can be used to treat a wide-spectrum of acute and chronic inflammatory diseases.

SUBMITTER: Dinarello CA 

PROVIDER: S-EPMC7597638 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature