Overview of Interleukins

Since the discovery of IL-1 in 1977, approximately 200,000 published articles have referred to ILs. The name "interleukin" was chosen in 1979, to replace the various different names used by different research groups to designate interleukin 1 (lymphocyte activating factor, mitogenic protein, T-cell replacing factor III, B-cell activating factor, B-cell differentiation factor, "Heidikine").Secreted proteins that bind to their specific receptors and play a role in the communication among leukocytes are named ILs. ILs are assigned to each family based on sequence homology and receptor chain similarities or functional properties. Usually, ILs contain the following families:

IL-1 Family
IL-6 Family
IL-10 Family
IL-12 Family
IL-17 Family
Other Interleukins

Interleukin-17 (IL-17) family

The IL-17/IL-17 receptor family is the newest and least understood of the cytokine subclasses.

Composed of ligands IL-17A-IL-17F and receptors IL-17RA-IL-17RE, these cytokines have many

unique structural and functional features. Members of this family have a highly conserved C-terminus containing a cysteine-knot fold structure. Most IL-17 proteins are secreted as disulfide-linked dimers, with the exception of IL-17B, which is secreted as a non-covalent homodimer.

Interleukin 12 (IL-12) family

The interleukin 12 (IL-12) family is unique in having the only heterodimeric cytokines, including IL-12, IL-23, IL-27 and IL-35. This family also has many molecular and functional characteristics that provide unique opportunities for positive and negative feedback control, and some additional features may still be identified. IL-12 is composed of p35 and p40 subunits. IL-23 is composed of the IL-12p40 subunit and the IL-23p19 subunit, which shares homology with IL-12p35. IL-27 is composed of EBI3/IL-27B and p28. IL-35, a novel member of IL-12 family, is composed of the IL-12p35 and EBI3 subunits. IL-35 is secreted by regulatory T cells, and suppresses inflammatory responses of immune cells.

Interleukin-10 (IL-10) family

The IL-10 superfamily is highly pleiotropic. Its members are linked together through genetic similarity and intron-exon gene structure. Significant commonality exists not only through shared

receptors but also through conserved signaling cascades. However, its members mediate diverse activities, including immune suppression, enhanced antibacterial and antiviral immunity, antitumor activity, and promotion of self-tolerance in autoimmune diseases.

Interleukin-6 (IL-6) family

IL-6, IL-11, IL-31 belong to the IL-6 family of cytokines. Inclusion in the IL-6 family is based on a helical cytokine structure and receptor subunit makeup. Members of the IL-6 family of cytokines activate the signal transducing receptor protein, glycoprotein 130 (gp130). As they share a common signal transducer, IL-6 family cytokines display both unique and overlapping biologic activities on multiple hematopoietic lineages. IL-6 family binding to the gp130 alpha subunit induces homodimerization and subsequent activation of Janus kinases (JAK), followed by activation of signal transducers and activators of transcription (STAT1 and STAT3).

Interleukin-1 (IL-1) family

The Interleukin 1 (IL-1) family is a group of 11 cytokines, which plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults. All of the members of IL-1 family, except of IL-1Ra, are first synthesized as a precursor protein, which means it is synthesized as a long form of protein which has to be proteolytically cleaved to a shorter, active molecule, which is generally called mature protein. IL-1 family precursors do not have a clear signalpeptide for processing and secretion and none of them are found in the Golgi, they belong to so-called leaderless secretory protein group. The similar feature of IL-1α and IL-33 is that their precursor forms can bind to their respective receptor and can activate signal transduction. But this is not a common feature for all IL-1 family members, since IL-1β and IL-18 precursor forms do not bind their receptors and require proteolytic cleavage by either intracellularcaspase-1 or extracellular neutrophilic proteases.

Introduction of Cytokines

What are Cytokines

Cytokines, a large group of soluble extracellular proteins or glycoproteins, are key intercellular regulators and mobilizers. Cells of the immune system communicate with one another by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to coordinate appropriate immune responses. They are now seen to be crucial to innate and adaptive inflammatory responses, cell growth and differentiation, cell death, angiogenesis and developmental as well as repair processes.