|IL-2 and HIV | type I IFN and arthritis | recombinant cytokine research|
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interleukin-2 and treatment of HIVInterleukin-2 as treatment for HIV
In deciding which recombinant cytokines are suitable for manufacture by transgenic plants, one must ask what major diseases may be treated by the cytokine in question. Research has already been done on expressing interleukin-2 (IL-2) in plants. This particular cytokine has come into some importance for the treatment of one of the biggest immunodeficiency causative agent of all: HIV.
HIV is characterised as a virus that attacks CD4+ helper T cells. It has been noticed that IL-2 levels are reduced in patients whose CD4+ T cells no longer proliferate in response to either mitogens or antigens, as they should. Increasing IL-2 through ectopic means have been shown in randomised controlled trials to have an additional beneficial effect in HIV-1 patients who are already undergoing highly active antiretroviral therapy (HAART), as opposed to patients who are undergoing HAART alone. These studies show that IL-2 treatment can significantly increase CD4+ T cell counts, decrease serum HIV RNA concentrations, and limit the negative disease effects of immune activation. The randomised controlled trials also demonstrated a nonsignificant 43% reduction in disease progression under IL-2 treatment. Treating patients with IL-2 is quite different from using a vaccine since IL-2 is a natural human immunological molecule, not foreign viral particle or an antigen, and therefore very safe.
Although it is not clear yet what are the mechanisms by which IL-2 combats HIV, it is theorised that IL-2 decreases CD4+ T cell turnover and prolongs the T cell's life, thus leading to increased CD4+ T cell numbers overall. The benefit of this treatment over HAART is that although HAART slows down the progression of HIV, it is unable to reconstitute the immune system like IL-2 may be able to. However, studies have yet to be done on how IL-2 acts alone in HIV therapy aside from HAART, and in conjunction with other cytokine treatments.
This cytokine has been expressed in various plant systems already, including the potato microtuber. Park et al has managed, using a tissue-specific patatin promoter, to express relatively high amounts of IL-2 in the potato microtuber tissue. Particularly, the use of the patatin promoter resulted in higher expression levels than obtained with the traditional CaMV 35S promoter. Expression levels of the gene were consistent and averaged 200g per potato. Furthermore, the human IL-2 was proven to be biologically active and able to stimulate the proliferation of IL-2 dependent cells (CTLL-2).
This study shows that IL-2 can be expressed in edible tissue, no less, which may open up venues to easy treatment. It also shows that high expression levels are attainable with the potato microtuber system, which is significant from an industrial perspective, in which efficient manufacture must be managed. Unfortunately no in vivo tests have been performed yet on the product itself.
references1) Cochrane A. Personal communication on "HIV". February 2006.
2) Vento S, Cainelli F, Temesgen Z. Interleukin-2 therapy and CD4+ T cells in HIV-1 infection. Lancet 2006, 367: 93-5.
3) Emery S, Capra WB, Cooper DA, Mitsuyasu RT, Kovacs JA, Vig P, Smolskis M, Saravolatz LD, Lane HC, Fyfe GA, Curtin PT. Pooled analysis of 3 randomized, controlled trials of interleukin-2 therapy in adult human immunodeficiency virus type 1 disease. J Infect Dis 2001, 183: 679-80.
4) Park Y, Cheong H. Expression and production of recombinant human interleukin-2 in potato plants. Protein Expr Purif 2002, 25: 160-5.