1. INTERFERON
PRESENTER- DR. CHINMAYA DASH

2. INTRODUCTION
•
In 1957 Isaacs and Linderman described a factor that have the
property of viral interference.
• Research has revealed diverse mechanism of action include
antiviral, immune enhancing and cytostatic activities.

3. Definition
Interferons (IFNs) are naturally occurring cytokines
with antiviral, immunomodulatory and antiproliferative
properties.
• First cytokine to be recognized

4. CLASSIFICATION
A. In 1980, nomenclature was formally adopted classifying IFNs into
three categories
Based on Antigenic Specificity:IFN categories
Earlier Designation
Alpha
(α)
Leukocyte
Beta
(β)
Fibroblast
Gamma ( )
Immune IFN
B. Their ability to bind to common Receptor Types :(Divided into TWO groups )

5. IFN
Types
IFN
Categories
Receptors
Prototypic cell of
Origin
Type-I
Alpha (α)
I
Leukocyte
Beta
I
Fibroblast
Omega ( )
I
Leukocyte
Tao ( )
I
Ovine Trophoblast
Gamma-
II
T-Cell
NK-Cell
Type-II
(β)

6. Properties
Alpha
Beta
Gamma
Current Nomenclature
IFN-α
IFN-β
IFN-
Former Designation
Leukocyte
Fibroblast
Immune
Interferon
Type Designation
Type I
Type I
Type II
No. Of Genes that code for Family
≥20
1
1
Principal Cell Source
Most Cell
Types
Most cell Types Lymphocytes
Inducing Agent
Viruses;
dsRNA
Viruses;
dsRNA
Mitogens
Stability at pH 2.0
Stable
Stable
Labile
Homology with IFN-α
80-95%
30%
<10%
Chromosomal location of genes
9
9
12
Size of secreted protein (Number of
amino acids)
165
166
143
IFN receptors
IFNAR
IFNAR
IFNGR
Chromosomal location of IFN receptor
genes
21
21
6

7. Important Features :• First recognized by their ability to interfere with viral
infections in cultured cells.
• Does not protect the virus infected cell that produces it.
• Itself is not the antiviral agent.
It moves to other cells where it induces an antiviral
state.(By inhibiting viral replication)
• Almost all cell types produce IFN-α &β and
IFN- are produced in T-cells and NK-Cells

8. INDUCTION AND ACTIVATION OF IFNs
A. IFN-α & β
(Type-I- IFNs)
When prototypic cell of origin is exposed to
-Viruses
-Double stranded RNA
-Polypeptides And
- Cytokines
B. IFN(Type-II- IFNs)
Following a number of immunological stimuli
including :-T-cell specific antigen
-Staphylococcal enterotoxin -A And
-Mitogens ( Phyto haemagglutinin ,Phorbol Ester
etc)

9. MODE OF ACTIVATION OF IFN STIMULATED GENES(ISGs):IFN binds with the respective
IFN-Receptors(IFNRs)
Oligomerization of the receptor followed by
phosphorylation of the tail of receptor
molecule
Phosphorylated stat ( Signal Transducers
and activators of transcription ) released from
the receptor molecules and translocate to the
nucleus
Activation of trancription of
IFN-Stimulated gene. This results in
synthesis of several enzymes

10.  These enzymes instrumental in development of the
antiviral state.
 dsRNA dependent protein kinase, PKRPhosphorylates and inactivates cellular initiation factor elF-2 ,
thus prevents viral protein synthesis
 2-5A synthetase (Oligonuceotide Synthetase)Activates a cellular endonuclease RNase L -» Degrade mRNA
 Phosphodiesterase- inhibits peptide chain elongation
 Nitric oxide synthetase, which is induced by IFN- in
macrophages
Fail to reveal why the antiviral state acts selectively against viral
mRNA and not cellular mRNA

12. BIOLOGICAL PROPERTIES
A. Properties of IFN α & Th1-Differentiation
Growth Inhibition
T-CELLS
IFNproduction
IL-1
Production
Proliferation
NK-CELL/
MACROPHAGES
IFN-α
&
ANTIANGIOGENIC
TUMOR CELLS
 MHC-I
expression
 Tumor
specific
antigenic
expression
Adhession
molecule
expression
Direct
cytostatic effect

13. B. Properties of IFN- :Increased Activation
T-CELLS
MHC ClassII
upregulation
APC/
MACROPHAGES
IFN-
ANTIANGIOGENIC
TUMOR CELLS
• MHC-I
upregulation.
•Decreased
proliferation

14. APPLICATIONS
A. Therapeutic Applications:Used to treat several neoplastic and non neoplastic
diseases.
Clinical indications of INF as follows:i.
Neoplastic Diseasesa. Lymphoma-
Non Hodgkin’s Lymphoma (NHL)
Follicular Lymphoma
b. Hematopoetic MalignaciesHairy Cell Leukemia
Chronic Myeloid Leukemia(CML)
c. CarcinomaRenal Cell Carcinoma (RCC)
Melanoma

15. ii. Non Neoplastic Diseasesa. Chronic Hepatitis B InfectionIFN-α / Peg IFN-α with Nucleoside Analogues
(Lamivudin, Adefovir,Tenofovir etc)
b. Chronic Hepatitis C InfectionStandard IFN and the combination of
Peg INF-α2a or 2b with or without Ribavirin therapy
c. Condyloma AcuminataIntralesional INF-α2b in previously resistant to
Podophyllum

16. TYPE
FDA- APPROVED INDICATIONS
IFN-α2a
-NHL, Hairy Cell Leukemia, CML
-AIDS related KS, Chronic Hepatitis-C
IFN-α2b
-Follicular Lymphoma, Hairy Cell
leukemia, AIDs related KS, Malignant
melanoma,
-Condyloma acuminata, Chronic
hepatitis B, Chronic hepatitis C
IFN-αn3
-Condyloma acuminata
IFN- β1a
-Relapsing remitting Multiple Sclerosis
IFN-β1b
-Relapsing remitting Multiple Sclerosis
IFN-
-Chronic Granulomatous Disease

17. B. Preventive Application-
Common Cold (Rhinovirus infection)Intranasal IFN-α2

18. C. Diagnostic Application:-
T Cell based interferon gamma (IFN- ) assay (IGRAs) for
Mycobacterium tuberculosis specific antigens
Helps in screening for Latent (LTBIs) and active tuberculosis
infection.

19. VIRUS MECHANISMS TO COUNTERACT INTERFERON
 Specific viral proteins may block induction of expression
of IFN
( Herpesvirus, Papilloma virus, Hepatitis C virus, Rota virus)
 May block the activation of the key PKR protein kinase
( Adenovirus, Herpes viruses)
 May activate a cellular inhibitor of PKR
( Influenza, Poliovirus)
 May block IFN induced signal transduction
(Adenovirus, Herpes virus, Hepatitis B Virus)
 May neutralize IFN- by acting as a soluble interferon receptor
( Myxoma virus )

20. SIDE EFFECTS
 Depending upon the time interval between induction of
therapy and appearance of side effects/toxicities classified as-
 Acute Toxicities ( Occur usually between 3-6Hrs after
receiving IFN )
 Chronic Toxicities

21.  Clinically there are four major side effect groupsSIDE EFFECTS
I.CONSTITUTIONAL
Fatigue (70%-100%)
Anorexia(40%-70%), Weight loss, Fever, Myalgia,
Headache
II.
• Dizziness/Vertigo
NEUROPSYCHIATRIC •Mood Disorder-( Confusion, pathological depression)
(upto 30%)
•Neuro endocrine disturbance( Perturbation of hypothalamo thyroid adrenalin axis)
III.HEPATIC
Transamnitis
IV.HEMATOLOGICAL
•Thrombocytopenia
•Anemia
•Leukopenia
(The severity of side effects)
α
(Dose and Duration of IFN therapy.)

22. REFERENCES
• Jonasch E and Haluska FG. Interferon in Oncological Practice:
Review of Interferon Biology, Clinical Applications, and Toxicities.
Oncologist 2001;6(1):34-55.
• Rijckborst V and Janssen Harry L.A. The Role of Interferon in
Hepatitis B therapy. Curr Hepatitis Rep 2010;9:231-238
• Kanda T, Imazeki F and Yokosuka O. New Antiviral Therapies for
Chronic Hepatitis C. Hepatol Int 2010;4:548-561
• Yoshihiro et al .Comparison of T Cell Interferon- y Release Assays
for Mycobacterium tuberculosis – Specific Antigens in Patients with
Active and Latent Tuberculosis. Lung 2010;188:283-287
• Hayden FG and Gwalthey JM jr. Intranasal interferon-alpha 2
treatment of experimental rhinoviral colds. J Infect Dis. 2003
Aug;150(2):174-80.

23. THANK
YOU