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.
