Treating Inflammation by Blocking Interleukin-1 in a Broad Spectrum of Diseases

Blockade of the pro-inflammatory cytokine interleukin-1 (IL-1) is emerging as an effective approach for the treatment of an increasing number of diseases. Here, Dinarello and colleagues discuss the pathogenic roles of IL-1, present therapeutic strategies aimed at modulating the activity of this cytokine and review clinical trial data for multiple indications. Interleukin-1 (IL-1) is a highly active pro-inflammatory cytokine that lowers pain thresholds and damages tissues. Monotherapy blocking IL-1 activity in autoinflammatory syndromes results in a rapid and sustained reduction in disease severity, including reversal of inflammation-mediated loss of sight, hearing and organ function. This approach can therefore be effective in treating common conditions such as post-infarction heart failure, and trials targeting a broad spectrum of new indications are underway. So far, three IL-1-targeted agents have been approved: the IL-1 receptor antagonist anakinra, the soluble decoy receptor rilonacept and the neutralizing monoclonal anti-IL-1β antibody canakinumab. In addition, a monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α antibody are in clinical trials.