Interleukins

Discovery

The discovery of ILs began with the pathogenetic study of fever in the 1940s. IL-1 was first discovered as human leukocytic pyrogen that induced fever; it was then reorganized and renamed IL-1 in 1979. So far, more than 40 ILs have been identified in humans; ILs have been put in the order in which they were identified. IL-1, IL-2, IL-6, and IL-10 were cloned in 1984, 1983, 1986, and 1990, respectively. IL-6 is currently the most major and successful IL. Therapeutic agents targeting IL-6-mediated signaling are effective in rheumatoid arthritis, and applications are being extended to other settings of acute and chronic inflammation. Indeed, worldwide clinical trials of tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, have successfully proved its outstanding efficacy against rheumatoid arthritis, juvenile idiopathic arthritis, and Castleman disease, leading to the approval of tocilizumab for the treatment of these diseases.

Structure

IL-1α (159 aa residues) has a 12-stranded β-sheet structure, IL-2 (134 aa residues) has four antiparallel α helices, IL-6 (184 aa residues) has a four-helix bundle arranged in an up-up-down-down topology, and IL-10 (160 aa residues) has a topological similarity to interferon gamma. The primary structures of IL-1 α, IL-2, IL-6, and IL-10 are conserved in vertebrates. ILs can be divided into four major groups based on the distinguishing structural features. However, their amino acid sequence similarity is very weak between the four groups (typically 15%–25% identity).

Receptors

IL receptors belong to the immunoglobulin superfamily, and could be categorized by their homologies. The receptors for IL-1α, IL-2, and IL-6 are the type I cytokine receptor, and the receptor for IL-10 is the type II cytokine receptor. In general, the binding of ILs with their receptors activates downstream signaling, including the Janus kinases (JAKs), tyrosine kinases (TYK), and STATs in target cells.

Antagonists

The IL-1 receptor antagonist (IL-1RA) and its modified version Anakinra are antagonists for the IL-1 receptor. Daclizumab and basiliximab are antagonists for the IL-2 receptor. Tocilizumab is an antagonist for the IL-6 receptor. The anti-IL-10 R antibody is an antagonist for the IL-10 receptor.

General Description

Interleukins (ILs) is a collective term for a group of cytokines. ILs mediate the communications in relation to immune reactions between immune cells as proinflammatory or antiinflammatory hormones. ILs are closely associated with inflammatory diseases and cancer.

Raw materials

Preparation Products