INTERFERONS

INTRODUCTION: The discovery of interferons came during the studies by Issacs and Lindermann on the ability of ONE VIRUS TO
INHIBIT THE MULTIPLICATION OF A SUPERINFECTING VIRUS. They found that influenza virus could induce the body’s cell to produce
and release a nonviral protein that could protect other cells against subsequent viral infection. They named the interfering protein as
INTERFERON.

Interferons are a family of secretory glycoproteins produced by most eukaryotic cells in response to a variety
of viral and nonviral inducers

Interferons are not single molecular species but consist of 3 families of protein molecules ( alpha, beta and gamma) whose
production can be induced in the body cells by different stimuli.

TYPES OF INTERFERON :

TYPE INDUCED BY CHARACTERISTICS CELL SOURCE

IFN-a: VIRUSES 19-24000 d B lymphocytes

leucocytic ds RNAs 13 subtypes macrophages
interferon microbial products less species specific
organic polymers
LMW substances

IFN-beta: SAME AS ABOVE 19-24000 d Fibroblast and epithelial

fibroblast more species specific cells
IFN
50,000 d
IFN- T lymphocytes very species specific T lymphocyte
gamma: Mitogens
immune Antigens
interferon Phorbol esters

INDICATIONS FOR INTERFERON ALPHA:

FDA approved indications Hairy cell leukemia, Kaposi sarcoma in AIDS, BCC, Hepatitis, Condyloma
acuminata

MALIGNANCIES Other leukemia and lymphoma, CTCL, Multiple myeloma, Cutaneous SCC, Carcinoid,
Renal cell carcinoma.

INFECTIONS Viral hepatitis B, Laryngeal papilloma, AIDS, Respiratory viral infection

IMMUNOREGULATORY Atopic dermatitis, LE, Behcet’s disease,

INHIBITION OF COLLAGEN KELOIDS
PRODUCTION

BIOLOGIC EFFECTS OF INTERFERONS:

action mechanism explanation

antiviral 1. induction of 2’-5’ adenylate synthetase Polymerises ATP to 2’-5’ linked oligomers ---
activates latent cellular endonuclease that degrades
viral + cellular RNA.
2. Induction of ribonuclease L Degrades single stranded viral RNA

3. induction of protein kinase P1 Inhibits t-RNA binding to ribosomes.

antiproliferative 1. induction of 2’-5’ adenylate synthetase Products inhibit MITOSIS, GROWTH FACTOR and
DOWN REGULATES c-myc, c-fos and certain c-ras
oncogenes
immunoregulat 1. induction of class I and II MHC
ory antigens
2. inceased numbers of NK cells
3. inhibits the production of Th2
cytokines such as IL-4,5,6.

USE IN CONDYLOMA ACUMINATA:

Because of the cost and multiple visits needed, this therapy should be used in highly motivated patients who have failed other
treatment modalities .
DOSE = 0.1 ml containing 1 million IU of IFN-2alpha per wart three times weekly for 3-4 weeks.

ADR: The adverse effects are generally dose dependant and remit either during continued therapy or after dose reduction. They are
also rapidly reversible on cessation of therapy.
 INFLUENZA LIKE SYMPTOMS: this is the most commonly associated ADR. Include fever, chills, myalgias, headache and
arthralgia. Prophylactic administration of acetaminophen or NSAIDS helps to prevent these effects.
 RHABDOMYOLYSIS : occurs with high dose (20 million )
 CVS EFFECTS: hypotension, dysrrthmia or tachycardia
 NEUROLOGIC AND PSYCHIATRIC EFFECTS: depression, spastic diplegia
 OTHERS: Gastrointestinal side effects such as N/V/dirrhoea. Neutralizing antibodies can develop.