Charles A Dinarello1,2. 1. Department of Medicine, University of Colorado Denver, Aurora, Colorado, 80045, USA. 2. Department of Medicine, Radboud University Medical Center, Nijmegen, HB 6500, The Netherlands.
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-1β). 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-1β (canakinumab, gevokizumab) and anti-IL-1α (xilonix). FINDINGS: Anakinra blocks the IL-1 Receptor type 1 (IL-1R1) and therefore blocks the activities of both IL-1α and IL-1β. Off-label use of anakinra is common for a broad spectrum of inflammatory diseases. Neutralization of IL-1β is used to treat hereditary autoinflammatory diseases but also atherosclerosis. Rilonacept reduces arterial wall inflammation in patients with chronic kidney disease. Neutralization of IL-1α 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.
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-1β). 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-1β (canakinumab, gevokizumab) and anti-IL-1α (xilonix). FINDINGS: Anakinra blocks the IL-1 Receptor type 1 (IL-1R1) and therefore blocks the activities of both IL-1α and IL-1β. Off-label use of anakinra is common for a broad spectrum of inflammatory diseases. Neutralization of IL-1β is used to treat hereditary autoinflammatory diseases but also atherosclerosis. Rilonacept reduces arterial wall inflammation in patients with chronic kidney disease. Neutralization of IL-1α 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.
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