INTERFERONS

Prepared by MELIS BECEREN

OUTLINE
 Discovery of Interferons
•1954, Nagano and Kojima
• discovered this soluble antiviral protein

• noticed that rabbit-skin previously inoculated with UV-inactivated virus

exhibited inhibition of viral growth when re-infected at the same site with live
virus.

•beganto characterize it by fractionation of the UV-irradiated viral

homogenates using an ultracentrifuge.

•1957, Isaacs and Lindenmann

•noticedan interference effect caused by heat-inactivated influenza virus on the
growth of live influenza virus in chicken egg membranes.

•coinedthe term "interferon," and today that specific interfering agent is known as
a "Type I interferon."
 What is Interferon?
•Naturally occurring proteins and glycoproteins

•Interferon is essential to the immune system

– helps protect us from the daily exposure to millions of germs that can
lead to serious infection

•Interferon is activated by the immune system when a virus attacks a cell .

•Interferon serves two important functions:

–signals neighbouring cells and triggers their resistance mechanisms

–activates other immune cells that kill invading pathogens

•Structurally, they are part of the helical cytokine family which are
characterized by an amino acid chain that is 145-166 amino acids long.
 General action of
Interferons
 Interferons are released by
macrophages, lymphocytes, and tissue
cells infected with a virus.

 When a tissue cell is infected by a

virus, it releases interferon.

 Interferon will diffuse to the

surrounding cells.

 When it binds to receptors on the

surface of those adjacent cells, they
begin the production of a protein that
prevents the synthesis of viral
proteins.

 This prevents the spread of the virus Figure1.Mechanism of Interferons’ activity

throughout the body.

 Types of Interferon
• Type I interferon
• Alpha (IFN-α) and beta (IFN-β)
• IFN-α is produced by leukocytes
• IFN-β is produced by fibroblasts

• Bind to a specific cell surface receptor

complex type 1 and both encoded on Figure 2. Alpha (IFN-α) interferon
chromosome 9.

• They have different binding affinities but

similar biological effects.

• Viral infection is the stimulus for alpha

and beta expression.
Figure 3. Beta (IFN-β) Interferon
 Types of Interferon
 Type II Interferon

◦ Interferon-gamma (IFN-γ) which is
an immune interferon produced by
certain activated T-cells and NK cells.
Figure 4. Interferon-gamma (IFN-γ)

◦ Bind to type 2 receptors and its genes are encoded on chromosome

12.

◦ Gamma production follows activation with immune and

inflammatory stimuli rather than viral infection.

◦ This production is controlled by cytokines secreted by interleukin

12 and 18.
 Therapeutic uses of Interferons
 Commercially available interferons are human interferons
manufactured using recombinant DNA technology.

 The mechanism of action of interferon is complex and is not

well understood.

 Interferons do not directly kill viral or cancerous cells; they

boost the immune system response and reduce the growth
of cancer cells by regulating the action of several genes that
control the secretion of numerous cellular proteins that
affect growth.
 Therapeutic uses of Interferons

 Although interferons are very similar they affect the body

differently. Therefore, different interferons are used for
different conditions.

◦ Interferon alphas are used for treating cancers and viral

infections.
◦ Interferon betas are used for treating multiple sclerosis.
◦ Interferon gamma is used for treating chronic
granulomatous disease.
 Recombinant forms of alpha interferon include:

• Alpha-2a drug name Roferon

To treat hairy cell leukemia, 
AIDS-related Kaposi's sarcoma,
and chronic myelogenous leukemia. 
Figure 5. Alpha-2a drug
• Alpha-2b drug name Intron A
Approved for the treatment of hairy cell leukemia, malignant melanoma,
condylomata acuminata, AIDS-related Kaposi's sarcoma, chronic
hepatitis C, and chronic hepatitis B.

• Alpha-n1 drug name Wellferon

• Alpha-n3 drug name AlferonN

For the treatment of genital and perianal warts caused by human
papillomavirus (HPV)

• Alpha-con1 drug name Infergen

 Recombinant forms of beta interferon include:

◦ Beta-1a drug name Avonex

◦ Beta-1b drug name Betaseron

 for the treatment of multiple sclerosis. 
Figure 6. Beta-1a drug

 Recombinant forms of gamma interferon include:

◦ Gamma-1b drug name Acimmune

 for the treatment of chronic granulomatous disease, and severe,
malignant osteopetrosis.
 Side effects of Interferons
 Common side effects of interferons:
fever, malaise, fatigue, muscle pains, vomiting, abdominal pain, diarrhea etc.

 High levels of interferons can cause kidney, liver, bone marrow and heart
toxicity.

 Tissue damage at the site of injection occurs with all of the interferons but more
commonly with interferon beta-1b and pegylated interferon alfa-2b.

 Depression and suicide have been reported among patients receiving interferons;

however, it is unclear whether depression and suicidal thoughts are caused by
the diseases being treated or the interferons themselves. Therefore, all patients
receiving treatment with an interferon should be observed for the development
of depression and suicidal thoughts.
 Conclusion
 Although interferons are very similar they affect the body differently.
Therefore, different interferons are used for different conditions.

 There may be lots of unknown mechanisms of action of interferon

worth researching for new developments therefore there is a lot of
room for future growth within this field.

 Recombinant DNA technology has provide a large supply of

interferons for treatment of disease and for research into its
therapeutic properties.
 
 REFERENCES
• Sidney, P. “The Interferons: 50 Years after Their Discovery, There Is Much More to
Learn,” Journal of Biological Chemistry 282, no. 28 (July 13, 2007): 20047 -20051
 
• Alm, Gunner V. “Role of Natural Interferon-alpha Producing cells (Plasmacytoid
Dendritic cells) in Autoimmunity.” Autoimmunity 36 (2003): 463-472.

• Goodsell, David S. “The Molecular Perspective: Interferons” The Oncologist 6

(2001): 374-375.

• Hertzog, Paul J. “Interferon-gamma: an overview of signals, mechanisms and

functions.” Journal of Leukocyte Biology 75 (2004): 163-179.

• http://pathmicro.med.sc.edu/mhunt/interferon.htm