OVERVIEW

Interleukin-1 (IL-1) and interleukin-6 (IL-6) are potent pro-inflammatory cytokines that are synthesized by many cells throughout the body and play major roles in inflammation and cell damage associated with excessive inflammation. IL-1 is increased in inflammatory conditions and appears to play a role in autoinflammatory and autoimmune diseases. Blockage of IL-1 production or inhibition of its activity decreases inflammatory responses and may be beneficial in many diseases associated with a heightened immune response such as rheumatoid arthritis, ankylosing spondylitis, gouty arthritis, osteoarthritis, juvenile idiopathic arthritis, Still disease, Familial Mediterranean fever, periodic fever and periodic syndromes. Blockage of IL-6 activity has similar clinical activity, although it has been assessed largely in inflammatory arthritidies. At least three IL-1 receptor antagonists have been approved for use in autoinflammatory conditions in the United States. In addition, a monoclonal antibody to the IL-6 receptor has been developed and shown to have beneficial effects in rheumatoid arthritis.

Recently, several of the interleukin receptor antagonists have been assessed as therapy of the advanced hyperinflammatory state of severe COVID-19. The rationale for their use is that advanced cases of SARS-Co-2 infection are associated with high circulating levels of IL-6 and other proinflammatory cytokines that contribute to the lung and systemic inflammation and injury. Several of these anti-cytokines have been granted emergency use authorization.

The interleukin receptor antagonists have been associated with rare instances of clinically apparent liver injury that is generally mild and resolves with discontinuation.

The interleukin receptor antagonists discussed in LiverTox include the following:

• Anakinra (Recombinant IL-1Ra)
• Canakinumab (Monoclonal antibody to IL-1β receptor)
• Rilonacept (Fusion protein of IL-1 receptor1 and IL-1R accessory protein with Fc region of IgG)
• Sarilumab (Monoclonal antibody to IL-6 receptor)
• Tocilizumab (Monoclonal antibody to IL-6 receptor)