Anti-inflammatory panacea? The expanding therapeutics of interleukin-1 blockade

Abstract

Purpose of review Blockade of IL-1 signaling is one of the oldest biologic therapies, yet the use of these agents is on the rise as the role of IL-1 activation is being recognized in a wide spectrum of inflammatory disorders. This review will cover established and emerging uses of IL-1 antagonism in rheumatic diseases. Recent findings Expanding off-label indications for IL-1 blockade include neutrophil-dominant skin diseases including pyoderma gangrenosum, hidradenitis supperativa, and pustular psoriasis. There is also increasing evidence for the use of IL-1 blockade in heart failure associated with rheumatic diseases. Somatic mosaicism in NLRP3 may explain the onset of later-in-life presentations of periodic fevers which are responsive to IL-1 blockade. Of importance, clinical response to anti-IL-1 therapy does not always denote protection from autoinflammatory disease complications such as macrophage activation syndrome or amyloidosis. Summary Indications for IL-1 blocking therapies will likely continue to broaden, but given the rarity of many rheumatic diseases which respond to such treatment, rigorous, large clinical trials for each indication are unlikely to occur. Thus, recommended use of these medications will often fall to the discretion of the astute physician. However, medication cost and hurdles of insurance approval, rather than drug efficacy, may be the primary limitation for more widespread use.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors)

“…IL-1R antagonist (IL-1Ra), also a member of the IL-1 family, acts as a competitive inhibitor as it binds to IL-1R with similar affinity as IL-1a and IL-1b. However, IL-1Ra lacks agonist activity, so contributing to the endogenous signalling regulation [2,3]. The therapeutic blockade of IL-1 has been the subject of clinical development for decades in view of the implication of the IL-1 family (particularly IL-1b) in the pathogenesis of autoimmune and autoinflammatory disorders, as well as in crystal deposition diseases ( Fig.…”

“…The therapeutic blockade of IL-1 has been the subject of clinical development for decades in view of the implication of the IL-1 family (particularly IL-1b) in the pathogenesis of autoimmune and autoinflammatory disorders, as well as in crystal deposition diseases ( Fig. 1) [3,4].…”

Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1βProduction

“…RA is a common inflammatory disease affecting small joints, and our knowledge about its pathogenesis is still incomplete. Nevertheless, elevated levels of IL-1 β and high expression of NLRP3 were detected from the serum and synovial tissue as well as in macrophages of RA patients [ 90 ].…”

Alzheimer Drug Trials: Combination of Safe and Efficacious Biologicals to Break the Amyloidosis-Neuroinflammation Vicious Cycle

“…combined with approved anti-neuroinflammatory agents such as the three classes of anti-IL-1 agents: anakinra, rilonacept, or canakinumab (Kahlenberg, 2016) and that these combinations should be administered early, in midlife, to symptom-free high-risk-for-AD individuals. We recommend safe biologicals from both classes of agents.…”