Treating inflammation by blocking interleukin-1 in humans

Abstract

IL-1 is a master cytokine of local and systemic inflammation. With the availability of specific IL-1 targeting therapies, a broadening list of diseases has revealed the pathologic role of IL-1-mediated inflammation. Although IL-1, either IL-1α or IL-1β, was administered to patients in order to improve bone marrow function or increase host immune responses to cancer, these patients experienced unacceptable toxicity with fever, anorexia, myalgias, arthralgias, fatigue, gastrointestinal upset and sleep disturbances; frank hypotension occurred. Thus it was not unexpected that specific pharmacological blockade of IL-1 activity in inflammatory diseases would be beneficial. Monotherapy blocking IL-1 activity in a broad spectrum of inflammatory syndromes results in a rapid and sustained reduction in disease severity. In common conditions such as heart failure and gout arthritis, IL-1 blockade can be effective therapy. Three IL-1blockers have been approved: the IL-1 receptor antagonist, anakinra, blocks the IL-1 receptor and therefore reduces the activity of IL-1α and IL-1β. A soluble decoy receptor, rilonacept, and a neutralizing monoclonal anti-interleukin-1β antibody, canakinumab, are also approved. A monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α are in clinical trials. By specifically blocking IL-1, we have learned a great deal about the role of this cytokine in inflammation but equally important, reducing IL-1 activity has lifted the burden of disease for many patients.

Novel Noncompetitive IL-1 Receptor–Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth

“…At present there are three large molecule anti-IL-1 drugs approved for clinical use, as follows: the IL-1R antagonist Anakinra (Kineret), the soluble decoy receptor Rilonacept (Arcalyst), and the neutralizing anti-IL-1b mAb Canakinumab (Ilaris). As anticipated, these IL-1-targeting therapies inhibit all IL-1-signaling pathways, including NF-kB (19,20). However, NF-kB, a major transcription factor for proinflammatory cytokines including IL-1, conveys important physiological roles such as cytoprotection and immune surveillance, particularly relevant in the vulnerable fetus.…”

A new treatment for knee osteoarthritis: Clinical evidence for the efficacy of Arthrokinex™ autologous conditioned serum

“…Heightened interest has led to a broader understanding of the inflammatory process that causes synovitis, subchondral bone remodeling and hyaline cartilage destruction, the central pathobiologic feature of OA. Interleukin 1 (IL-1) has been implicated in many human pathological conditions 4 and is the chief mediator of OA-associated inflammation.…”

Etiology, Immunopathogenesis and Biomarkers in Behçet’s disease

“…Among the 11 cytokines in the family, IL1β is the principal pro-inflammatory cytokine, leading to the expression of many chemokines and secondary mediators of inflammation and upregulating innate immunity in response to infectious agents [66]. The levels of IL1β have been shown to be elevated in several studies [45,46,49,67,68], including in synovial fluids of BD patients [45,46].…”