Contact: to feature here

Thread Rating:
  • 1 Vote(s) - 1 Average
  • 1
  • 2
  • 3
  • 4
  • 5
Application of recombinant interferons in medical field
Cytokines belong to the group of proteins, which are usually regulatory in nature and maybe glycoprotein in some cases, produced by the body in minute amounts. Their main role can be seen in cell communication by the trigger of different signal transduction pathways within the cell after binding to the specific receptors on cell surface. They are usually produced by leukocytes and play major roles in the immune system such as haematopoiesis and inflammatory systems such as healing of wounds. Interferons belong to the class of cytokines that were discovered first. Wide range of interferons are secreted by different species, and in humans, 3 types of interferons have been studied- Interferon α, Interferon β and Interferon γ, which play important roles within the human body such as
a) Development of cellular resistance against viral attack,
b) Immune function regulation,
c) Growth and differentiation of different cell types, and
d) Sustenance of preliminary stages of pregnancy.

The interferons have potential medical applications due to their antiviral and anti-proliferatory activities as well as their ability in regulation of immune and inflammatory responses within the body. The production of interferons in minute quantities remained a drawback in their therapeutic applications. Hence, various techniques for their isolation from different sources were studied. The recombinant DNA technology has helped in the large-scale production of interferons for meeting the different medical needs by the recombinant expression of the interferons in the microbial organisms. However, various purification techniques are essential to remove the non-human substances from the produced interferons before the application of the recombinant interferons in medical purposes. Different types of interferons have been found to have different medical uses as given below:

a) Studies related to Interferon α (IFN- α) have shown its anti cancer properties. It has been associated with tumor regression in patients suffering from multiple myeloma, lymphoma as well as breast cancer. Recurrence of tumor growth after surgery was prevented by IFN- α in patients of osteogenic sarcoma. The development of recombinant IFN- α (rh IFN- α) by the cloning and expression of the genes encoding it has helped in the progress of the clinical studies related to IFN- α. The production of rh IFN- α is generally done in E.coli system. IFN- α have been shown to have anti-viral, immune-modulatory, and anti-tumour properties that has helped in its medical application. Various recombinant interferons have gained approval for marketing such as the PEGylated interferons (PEG IntronA and Viraferon Peg) and the interferon product, which is synthetic known as Infergen. rhIFN- αs have been found effective in the therapeutics for various viral conditions, of which viral hepatitis is one. IFN- α has been found potent to combat a number of diseases induced virally, AIDS being one of them. Hence, it is being appraised for different clinical trials.

b) Recombinant forms of IFN- β (rh IFN- β) have found successful medical application in the therapeutics of the disease affecting the nervous system known as multiple sclerosis that is relapsing and remitting in nature. Although the exact cause for the onset of the condition remains unknown, various factors have been implicated including genetic and environmental (possibly viral infection). Different rh IFN- β preparations have gained approval for medicinal purpose such as Betaferon, Betaseron produced in E.coli cells and Avonex, Rebif produced in the CHO cell lines. However, the exact mechanism by which the IFN- β induces its therapeutic effect remains unclear and it is hypothesised that the down-regulation of the pro-inflammatory response may be the responsible factor.

c) IFN- γs have found medical application in the treatment of a rare genetic condition known as the chronic granulomatous disease (CGD), in which the phagocytic cells are incapable of being effective against the foreign invaders such as bacteria and protozoa and hence make the body susceptible to various infections that may be life threatening. Rh IFN- γs have been produced in E.coli cells. IFN- γ have been found effective in the stimulation of the phagocytic activity in the patients suffering from various diseases such as cancer, lepromatous leprosy (caused by the bacterium Mycobacterium leprae) as well as AIDS.

Although, interferons have found successful application in medical field, their administration is also accompanied by some side effects like most drugs. The characteristic flu-like symptoms is observed in the administration of the interferons, however in some cases, their administration is accompanied by serious side effects like
a) autoimmune reactions or nervous and cardiac disturbances in IFN- α,
b) hypersensitivity, menstrual disorders, suicidal thoughts and depression in IFN- β, and
c) Heart failure, CNS complications, and metabolic complications in IFN- γ.

However, prediction of the possible side effects is impossible without administration. Hence, careful monitoring of the concerned patients after administration of the interferons is essential before the treatment can be suspended due to the development of unwarranted, serious side effects.
Like Post Reply
Interferon Mode of Action:

Interferons are released by macrophages, lymphocytes and tissue cells infected with a virus. When interferon reacts with the interferon receptors of a cell, the cell enters in a state called interferon-induced antiviral state. In this state, a rapid degradation of mRNA occurs if the cell is infected by any virus. Interferon induces in cells the production of 2, 5-adenosine polymerase. When such a cell is infected by a virus, the 2, 5-adenosine polymerase is activated to produce 2, 5-adenosine polymerase, which in turn activates pre-existing, but inactive, molecules of ribonuclease-L. Activated ribonuclease-L degrades all mRNAs (of host as well as virus origin) present in the cell bringing the protein synthesis to a halt in such cells. This interferes with multiplication of the virus so that virus infection is either stopped or sufficiently slowed down to allow the production of adequate antibodies against the invading virus. The protection due to interferons is nonspecific in that interferon induced by any one virus will provide protection against all viruses. It is possible that interferons modify ribosomes so that they no longer translate viral mRNAs, although they are fully capable of translating mRNAs of the host origin.

Interferons enhance the cytotoxic activity of natural killer cells (NK cells) which are a type of lymphocytes identifiable as large granular lymphocytes. Interferons are known to inhibit growth of some types of tumors; most of these tumors are also responsive to chemotherapy.

Production of recombinant interferons (General protocol):

Interferons are produced from human leucocytes isolated from donor blood and cultured in vitro, and from mouse fibroblast cultures. Large scale (1000 l to 10,000 l) cell cultures are infected with Sendai virus, and incubated for 24 hr, after which the supernatant (clear fluid) is collected, centrifuged, and used for interferon isolation. The amount of interferon recovered is relatively small (1g interferon of low purity from leucocytes separated from blood of about 90,000 donors), and the normal leucocytes are difficult to culture preventing scaling up from relatively small inoculate.
Like Post Reply

Possibly Related Threads…
Last Post

Users browsing this thread:
1 Guest(s)

Application of recombinant interferons in medical field11