Interleukin class 2 cytokines

Besides direct apoptosis effectors, there are a number of other diugs which influence the above explained apoptosis pathways more indirectly. This class of diugs includes molecules which inhibit survival pathways like e.g. the Ras/Raf kinase pathway, the NF-kB pathway and many others. Also inhibitors of survival cytokines which are sometimes produced by cancer cells in an autocrine fashion can render cells susceptible to apoptosis and, hence, effective cancer therapy. These include, but are not limited to, ligands for dependence receptors and cytokines like e.g. interleukin-4. 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

Cytokine receptors are a group of structurally related receptors, which couple to the JAK-STAT pathway. Cytokine receptors function as homodimers or heterooligomers. They are divided into two main subclasses, class I, which contains receptors for a variety of hematopoietic growth factors and interleukins and class II, which contains receptors for interferons and interleukins 10, 20/24 and 22. 

These propyretic factors belong to the class of immunomodulatory polypeptides called cytokines. Most prominent among these are interleukins (IL)-1 (3... 

The coupling of superantigen—major histocompatibility complex class II to T-cell receptor swifdy results in cell-signaling cascades. ° These staphylococcal toxins can increase levels of phosphatidyl inositol from quiescent T cells, such as other mitogens, as well as elicit intracellular Ca movement that activates the protein kinase C (PKC) pathway important for interleukin-2 (IL-2) expression. " IL-2 is intimately linked to T-cell proliferation. In addition to the PKC pathway, the protein tyrosine kinase (PTK) pathway is also activated by superantigens, leading to elevated expression of various proinflammatory cytokines. Staphylococcal superantigens also potently activate transcriptional factors NF-/IB (nuclear factor kappa B) and AP-1 (activator protein-1), which subsequently elicit the synthesis of proinflammatory cytokines. " " ... 

Just as interferons and interleukins are a subset of the class of molecules known as cytokines, in turn, cytokines are a subset of a larger family of proteins known as growth factors (see figure 6.3). Although not all growth factors are involved in regulation of the immune system, they are nevertheless protein messenger molecules that influence cell... 

Fig. 11.1. Principle of an immunological synapse. Possibilities for communication between B and T cells during an immune response. Antigenic peptides are presented by the MHC complex class II at the surface of the B cell. The antigens are recognized and bound by T cell receptors of the T cell. The T cell receptor is activated and sets a signal chain in motion that leads to activation of the expression of cytokines, such as IL-2. The cytokine is secreted, and binds and activates a cytokine receptor on the B cell. TNFa is shown as another example of a ligand-receptor system. TNFa communicates, as a membrane-bound ligand, with a corresponding receptor on the surface of the B cell. The interactions shown take place in a narrow spatial region between B and T cells, which is why this system is referred to as an immunological synapse. TNF tumor necrosis factor MHC major histocompatibility complex IL-2 interleukin 2.

Another cytokine class used as a biopharmaceutical is interleukin (IL), which consists of at least 25 different subtypes (IL-1 to IL-25). Except for IL-1, most interleukins are glycosylated and have a molar mass in the range of 15-30 kDa. IL-2 is the most well studied interleukin, and its recombinant form is approved for the treatment of renal cell carcinoma. Since the absence of glycosylation does not affect its biological activity, rIL-2 is produced in genetically engineered E. coli. 

Acute-phase proteins are a class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-phase reaction (or acute-phase response). In response to injury, local inflammatory cells secrete a number of cytokines into the bloodstream, the most notable of which are the interleukins (IL-1, IL-6, IL-8) and TNF-a. The liver responds by producing a large number of acute-phase reactants or reducing the production of others. 

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