Interleukins (IL) are a group of naturally occurring proteins that mediate communication between cells. They are a subset of a larger group of cellular messenger molecules called cytokines, which are modulators of cellular behavior. These molecules act as immunomodulatory autocrine, paracrine and endocrine signalling molecules and are involved in the regulation of a variety of physiological and pathological conditions such as normal and malignant cell growth, recognition and elimination of pathogens by immune cells and are particularly important in stimulating immune responses such as inflammation.
Determining the exact function of a particular cytokine is made complicated by the influence of the producing cell type, the responding cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterization.
Interleukins can be distinguished from chemokines, the main function of which is to direct immune cells to the site of inflammation via chemotaxis and interferons (IFNs), which predominantly mediate cellular response to viral infection. Despite attempts to separate these three groups based on function, there is a degree of overlap.
All interleukins are pleiotropic and act on a variety of cell types. In addition, ILs can stimulate or block the production of other cytokines with similarly pleiotropic activities. The function of the immune system depends largely on these proteins and rare deficiencies of a number of them are all featuring in autoimmune diseases or immune deficiency. Most interleukins are synthesized by helper CD4 T lymphocytes, monocytes, macrophages, and endothelial cells.
Interleukins are not stored within cells but are instead secreted rapidly, and briefly, in response to a stimulus. Once an interleukin has been produced, it travels to its target cell and binds to it via a receptor molecule on the cell’s surface. This interaction triggers a cascade of signals within the target cell that ultimately alter the cell’s behavior. The response of a particular cell to these compounds depends on the ligands involved, specific receptors expressed on the cell surface and the particular signaling cascades that are activated.
The human genome encodes more than 50 interleukins and related proteins. The known ILs can be divided into four major groups based on distinguishing structural features.
These groups include
However, their amino acid sequence similarity is quite weak (typically 15–25% identity) which makes the classification rather wide. In addition, there are several ILs that do not fit into any of the above groups, due either to their unique structural features or lack of structural information.
Since interleukins have such a pivotal role in the mediation of the physiological response to infection and also contribute significantly to the functional changes that accompany a particular disease or disorder, it has become evident that they represent a group of proteins with potential importance as therapeutic targets.
Their profound linkage to host defence and disease-causing mechanisms through modulation of inflammatory and immune responses has proven them ideal for developing novel therapies involving either ILs themselves or their antagonists especially in the range of malignant, infectious and inflammatory diseases.
Another advantage is the relatively simple MOA where these proteins bind to specific receptors which triggers a reaction, offering a multitude of therapeutic possibilities to act on either the interleukin or receptor in a antagonistic or agonistic manner.
The introduction of recombinant technology has made many of these molecules available in large quantities and has brought up the possibility of large-scale testing for therapeutic potential. Several interleukins and inhibitory molecules have been evaluated for clinical efficacy and safety in clinical studies, and the clinical application of these new biotherapeutic agents has already resulted in some successful treatments;
Many more have been developed, are currently in development or in different stages of clinical trials. These therapies are an increasingly important class of drugs in the treatment and management of many diseases and the main message is that interleukin therapeutics is a rapidly growing field with major pharmaceutical impact.
Introducing these new potential targets does challenge the research community by the extraordinary complexity of their biological activities. Since the interaction between a protein and its receptor triggers a cascade of signals and the response of the cell is dependent on this pathway activation, it is essential to be able to identify and quantify this reaction. By utilizing functional and biologically relevant cell based assays - where both the binding event as well as the resulting signaling cascade can be established and translated into a quantifiable units - these reactions can be mapped, monitored and measured.
Scientists developing cell-based assays for these high-profile drug targets face several challenges, including long development time, low specificity and low throughput due to long and cumbersome assay protocols. The iLite Platform offers cell-based assays that enable the study and targeting of human interleukin proteins and their receptors, while addressing these issues. The assays are designed to be highly specific, with simple and quick protocols, large signal to noise ratio, high matrix tolerance and have high reproducibility. This enables their broad usage in applications such as functional screening, functional characterization, QC lot release (potency) assays and neutralizing antibody studies.