INTERFERONSINTRODUCTION: The discovery of interferons came during the studies by Issacs and Lindermann on the ability of ONE VIRUS TOINHIBIT THE MULTIPLICATION OF A SUPERINFECTING VIRUS. They found that influenza virus could induce the body’s cell to produceand release a nonviral protein that could protect other cells against subsequent viral infection. They named the interfering protein asINTERFERON.
Interferons are a family of secretory glycoproteins produced by most eukaryotic cells in response to a varietyof viral and nonviral inducers
Interferons are not single molecular species but consist of
of protein molecules ( alpha, beta and gamma) whoseproduction can be induced in the body cells by different stimuli.
TYPES OF INTERFERON
: TYPE INDUCED BYCHARACTERISTICSCELL SOURCEIFN-a:leucocyticinterferonVIRUSESds RNAsmicrobial productsorganic polymersLMW substances19-24000 d13 subtypesless species specificB lymphocytesmacrophagesIFN-beta:fibroblastIFN SAME AS ABOVE19-24000 dmore species specificFibroblast and epithelialcellsIFN-gamma:immuneinterferon T lymphocytesMitogensAntigensPhorbol esters50,000 dvery species specificT lymphocyteINDICATIONS FOR INTERFERON ALPHA:FDA approved indications
Hairy cell leukemia, Kaposi sarcoma in AIDS, BCC, Hepatitis, Condylomaacuminata
MALIGNANCIESOther leukemia and lymphoma, CTCL, Multiple myeloma, Cutaneous SCC, Carcinoid,Renal cell carcinoma.INFECTIONSViral hepatitis B, Laryngeal papilloma, AIDS, Respiratory viral infectionIMMUNOREGULATORYAtopic dermatitis, LE, Behcet’s disease,INHIBITION OF COLLAGENPRODUCTIONKELOIDSBIOLOGIC EFFECTS OF INTERFERONS:actionmechanismexplanationantiviral1. induction of 2’-5’ adenylate synthetase Polymerises ATP to 2’-5’ linked oligomers ---activates latent cellular endonuclease that degradesviral + cellular RNA.2. Induction of ribonuclease LDegrades single stranded viral RNA3. induction of protein kinase P1Inhibits t-RNA binding to ribosomes.antiproliferative1. induction of 2’-5’ adenylate synthetaseProducts inhibit MITOSIS, GROWTH FACTOR andDOWN REGULATES c-myc, c-fos and certain c-rasoncogenesimmunoregulatory1.induction of class I and II MHCantigens2.inceased numbers of NK cells3.inhibits the production of Th2cytokines 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 othertreatment 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 arealso rapidly reversible on cessation of therapy.
INFLUENZA LIKE SYMPTOMS: this is the most commonly associated ADR. Include fever, chills, myalgias, headache andarthralgia. 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