Interferons

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: leucocytic interferon

VIRUSES ds RNAs microbial products organic polymers LMW substances

19-24000 d 13 subtypes less species specific

B lymphocytes macrophages

IFN-beta: fibroblast IFN

SAME AS ABOVE

19-24000 d more species specific

Fibroblast cells

IFNgamma: immune interferon

T lymphocytes Mitogens Antigens Phorbol esters

50,000 d very species specific

T lymphocyte

and

epithelial

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 PRODUCTION

COLLAGEN

KELOIDS

BIOLOGIC EFFECTS OF INTERFERONS: action mechanism antiviral

antiproliferative immunoregulat ory

1. induction of 2’-5’ adenylate synthetase

explanation

2. Induction of ribonuclease L

Polymerises ATP to 2’-5’ linked oligomers --activates latent cellular endonuclease that degrades viral + cellular RNA. Degrades single stranded viral RNA

3. induction of protein kinase P1

Inhibits t-RNA binding to ribosomes.

1. induction of 2’-5’ adenylate synthetase

Products inhibit MITOSIS, GROWTH FACTOR and DOWN REGULATES c-myc, c-fos and certain c-ras oncogenes

1. 2. 3.

induction of class I and II MHC antigens inceased numbers of NK cells 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.

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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

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OTHERS: Gastrointestinal side effects such as N/V/dirrhoea. Neutralizing antibodies can develop.