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introduction to recombinant cytokinesWhat are cytokines?
Of all immunological compounds, cytokines are probably the least well known to the public, and yet they play a pivotal role in both the adaptive and innate branches of immunity. Cytokines are proteins secreted as a response to some sort of external physiological insult, such as an infection or a wound. The immune system uses these molecules as sort of an inter-system signalling array, since within their many subclasses, cytokines are capable of triggering cell differentiation, immune response expansion, protection against viral infection, recruitment of other immune response molecules, inflammation, etc. This may sound like a very broad list, but in truth, cytokines are most often pleitropic (i.e. one cytokine can effect many results) and also biologically redundant (i.e. many cytokines can effect the same result).
To exemplify the activity of cytokines: during T helper cell activation, the T cell and professional antigen presenting cell (APC) in question will both release cytokines to determine or change the immune response profile of the body. The activated T cell will in response release more cytokines that affect other branches of the immune system, e.g. activating the macrophages of the innate immunity, recruiting other cells to the site of infection identified by the T cells, or inflaming the site of infection.
Cytokines and immunotherapy
Cytokines play a very large role in virtually every aspect of the immune system, and therefore lend themselves well to adaptation to immunotherapy. By manipulating cytokines in a patient, diseases can be controlled and treated. For example, naturally unbalanced levels of cytokines can cause autoimmune diseases like arthritis, in which the inflammatory cytokine TNF-α is especially prevalent. In creating monoclonal antibodies against TNF-α, arthritic inflammation can be controlled.
Conversely, the introduction of more cytokines to the system may help regulate an unhealthy process. IFN-γ has become a big player in the treatment of multiple diseases, and IL-12 has been shown to inhibit cancer progression. Recent research has also shown that IL-2 may be able to complement highly active antiretroviral therapy (HAART) against HIV by lowering serum HIV RNA levels and combating HIV's trademark destruction of CD4+ T cells. Hence, the suitability of using the body's natural immunological tools to battle autoimmune diseases and immunodeficiencies, and the subsequent interest in producing recombinant cytokines for medical use.
This section will deal largely with those recombinant cytokines that are prominent in research, lend themselves well to the treatment of autoimmune diseases, and are especially suitable for production in a modest industry.
references1) Fish, E. Personal communication on "cytokines". Feb 9, 2006.
2) Gutierrez-Ortega A, Avila-Moreno F, Saucedo-Arias LJ, Sanchez-Torres C, Gomez-Lim MA: Expression of a single-chain human interleukin-12 gene in transgenic tobacco plants and functional studies. Biotechnol Bioeng 2004, 85: 734-40.
3) Vento S, Cainelli F, Temesgen Z: Interleukin-2 therapy and CD4+ T cells in HIV-1 infection. Lancet 2006, 367: 93-5.