Colorectal polyposis and immune-based therapies: CYTOKINES AS IMMUNE MEDIATORS (Part 2)

In: Colorectal polyposis

31 Aug 2012

 TH1 helper cells

Triggering the CD8+ activation pathway of TH1 helper cells produces a dramatic increase in proinflamma-tory cytokines, which then act on effector molecules to carry out antitumour activity. Two of the most crucial of these cytokines are interleukin (IL)-2 and IL-12, both of which function in the CD28-CD80 receptor-ligand system to promote antitumour cytotoxic responses . IL-12, a het-erodimeric molecule composed of two bioactive chains, is secreted mostly by macrophages. B cells, monocytes, dendritic cells, Langerhans cells and keratinocytes may also secret it. IL-12 plays an important role in developing the cytotoxicity of CTLs by upregulating the mRNA expression of the effector molecules granzyme (granzyme B) and perforin.

IL-12 receptors are located on CD4+ and CD8+ T cells and, in addition to upregulating the activity of these cells, IL-12 induces the production of interferon-gamma (IFN-y), a cytokine that functions with IL-12 to enhance T cell antitumour immunity. The role of IL-2 appears to act synergistically with IL-12 to upregu-late natural killer (NK) cells and to substitute for CD8+ signalling during CTL development. IL-2 and IL-12 are able to enhance the ability of NK cells to lyse neuroblastoma and osteosarcoma cells in vitro and have been implicated in the regression of certain cancers .

In addition to IL-2, IL-12 and IFN-y, much attention has been given recently to the antitumour immune effects of tumour necrosis factor-alpha (TNF-a) and the TNF-related apoptosis-inducing ligand (TRAIL). TNF-a is a well-known cytokine that has been implicated in a wide spectrum of diseases, including sepsis, diabetes, cancer, osteoporosis, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease . The cytokine, first described a century ago, is a homotrimer of 157 amino acid subunits, whose cDNA has been cloned and expressed to produce recombinant TNF-a. You can finally spend less time to discover cheap asthma inhalers always paying lower prices.

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