IL1-Ra at a glance

Interleukin-1 (IL-1) - a typical proinflammatory cytokine

Interleukin-1 has various biological properties that are involved in proinflammatory reactions of a cell. IL-1 induces and promotes the formation of cyclooxygenase 2 (Cox-2) and inducible nitric oxide synthase (iNOS). Cells that are treated with IL-1 therefore produce prostaglandin E2 (PGE2) and nitric oxide (NO). IL-1 also causes the formation of adhesion molecules on endothelial cells and other cells in the joint space. In patients with rheumatoid arthritis, IL-1 is present in the synovia in increased concentrations compared to the normal population. The interleukin-1 gene family consists of 7 components, of which IL-1 alpha, IL-1 beta and the receptor antagonist IL-1Ra have already been characterized in more detail.

Interleukin-1 receptor antagonist

The IL-1 receptor antagonist is an endogenous antagonist of IL-1 that occurs in the body. It competitively inhibits the effect of IL-1 alpha and IL-1 beta by binding to the IL-1 receptor and blocking it. IL-1 alpha and IL-1 beta can no longer dock and signal transmission into the cell interior (signal transduction cascade) no longer takes place. The receptor antagonist thus prevents the pro-inflammatory effect of IL-1.

Patients with rheumatoid arthritis have increased amounts of IL-1 in the plasma. The amounts of IL-1Ra produced by the body are not sufficient to counteract the destructive effect of IL-1. The amount of IL-1Ra is only about 1.2 to 3.6 times higher than that of IL-1. However, a ten to one hundred times higher concentration of IL-1Ra is required to block IL-1.

Molecular portrait of the IL-1 receptor antagonist (IL-1Ra)

The IL-1 receptor antagonist is synthesized as a precursor protein with 177 amino acids. This contains a signal sequence of 25 amino acids. The mature protein consists of 152 amino acids and is glycosylated.

IL-1Ra can be either glycosylated or non-glycosylated. In vivo, IL-1Ra is produced by monocytes, macrophages, neutrophils, keratinocytes and other epithelial cells. IL-1Ra has 30% amino acid sequence identity to IL-1 alpha and 19% to IL-1 beta.

Recombinant IL-1Ra 1ra for the treatment of rheumatoid arthritis (RA)

Anakinra corresponds to the non-glycosylated, natural version of IL-1Ra, with the exception of an additional N-terminal amino acid methionine.