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Viral infection - Interferon drugs

Category: Medicines

Type

Involuntary and voluntary

Introduction and description

 

As the explanation on Wikipedia was very clear and helpful, this has been used in the following explanation.  The pictures were chosen to give comfort

The body has its own mechanism of attacking and destroying pathogens which is based on interferons and killer T cells.  Killer T cells are destructive because they are the defence of last resort from the body’s point of view.  They kill the cell as well as the virus.  But interferons are different. 

Interferons (IFNs) are a group of signaling proteins made and released by host cells in response to the presence of pathogens. They are thus part of the immune system.  In a typical scenario, for example, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

IFNs belong to the large class of proteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. Interferons are named for their ability to "interfere" with viral replication by protecting cells from virus infections. IFNs also have various other functions: they activate immune cells, such as natural killer cells and macrophages; they increase host defenses by up-regulating antigen presentation by virtue of increasing the expression of major histocompatibility complex (MHC) antigens.

More than twenty distinct IFN genes and proteins have been identified in animals, including humans. They are typically divided among three classes: Type I IFN, Type II IFN, and Type III IFN. IFNs belonging to all three classes are important for the regulation of the immune system.

Viruses that resist

 

Many viruses have evolved mechanisms to resist interferon activity. They circumvent the Interferon response by

  • blocking downstream signaling events that occur after the cytokine binds to its receptor,
  • preventing further IFN production, and
  • inhibiting the functions of proteins that are induced by IFN
  • mutating genes (and thus protein).

Viruses that inhibit IFN activity include:

  • Viruses of the Flaviviridae family that possibly includes:
    • West Nile,
    • Yellow Fever
    • Japanese Encephalitis Virus (JEV),
    • Dengue type 2 virus (DEN-2)
    • Zika virus (ZIKV) an emerging arbovirus
  • Viruses of the herpesvirus family – there are at least five species of Herpesviridae
    • HSV-1 and HSV-2 (both of which can cause orolabial herpes and genital herpes),
    • Varicella zoster virus (which causes chicken-pox and shingles),
    • Epstein-Barr virus (which causes mononucleosis),
    • Cytomegalovirus
    • Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8)
  • Viruses of the Papillomaviridae family -  an ancient taxonomic family of non-enveloped DNA viruses, collectively known as papillomaviruses. Several hundred species of papillomaviruses have been identified. The Human papillomavirus (HPV) is one that is known to exhibit this ability
  • Viruses of the Polyomaviridae family. There are currently 13 species in this family, divided among 1 genera - type species Simian virus 40.  Also known as the Polyomavirus
  • Several poxviruses -   Vaccinia virus (VACV or VV), for example, is one. Vaccinia virus is the active constituent of the vaccine that eradicated smallpox
  • Viruses in the family Reoviridae -  There are currently 87 species in this family, divided among 30 genera, but it is not known yet how many have this ability.  The family includes Rotavirus
  • H5N1 influenza virus

There are more

The Class of Drugs

 

Interferon therapy was evolved in order to treat people who had these viruses.  The objective was to try to boost the interferon levels in order to fight the virus, in effect circumvent the viruses destructive action by adding more interferon.

But this rather simple thinking is now being called into question.  This paper explains the problem:

Type I IFNs are known to inhibit viral replication and mediate protection against viral infection. However, recent studies revealed that these cytokines play a broader and more fundamental role in host responses to infections beyond their well-established antiviral function. Type I IFN induction, often associated with microbial evasion mechanisms unique to virulent microorganisms, is now shown to increase host susceptibility to a diverse range of pathogens, including some viruses. This article presents an overview of the role of type I IFNs in infections with bacterial, fungal, parasitic, and viral pathogens and discusses the key mechanisms mediating the regulatory function of type I IFNs in pathogen clearance and tissue inflammation. PMID:  25747907

The drugs in the past have been used for a whole host of virus related diseases, they have been used to treat and control multiple sclerosis, and they have been used in combination with chemotherapy and radiation as a treatment for some cancers – such as hematological malignancy; leukemia and lymphomas including hairy cell leukemia, chronic myeloid leukemia, nodular lymphoma, and cutaneous T-cell lymphoma.  Patients with recurrent melanomas receive recombinant IFN-α2b. Both hepatitis B and hepatitis C are treated with IFN-α, often in combination with other antiviral drugs.  There is no doubt that in the very short term these drugs have helped, slightly elongating the person’s time of survival.  Biopsies of patients with hepatitis given the treatment show reductions in liver damage and cirrhosis.

 

But it is clear from the above that it has left the person open to other classes of infection.  Thus the person may not die of hepatitis, but they may die of some parasitic disease.

There is also a further complication.  It is now being realised that viruses actually fight each other in our systems.  In some respects our bodies are an amazing battleground of competing forces – friendly bacteria forming temporary alliances with not so friendly viruses in order to fight extremely unfriendly viruses.  Bacteria and viruses forming alliances with our immune system to fight parasites – and so on.  It is not a simple case of fighting one virus – you have to know what the politics of the body is at the time!

Great progress has been made in understanding immunity to viral infection. However, infection can occur in the context of co-infection by unrelated pathogens that modulate immune responses and/or disease. We have studied immunity and disease during co-infection with two unrelated viruses: Ectromelia virus (ECTV) and Lymphocytic Choriomeningitis virus (LCMV). …. We show that ECTV/LCMV co-infection results in decreased ECTV viral load and amelioration of ECTV-induced disease …..Thus, we provide evidence for bi-directional effects of viral co-infection that modulate disease and immunity.  PMID:  26099694

Thus although interferon drugs were invented with the best of intentions, they are not a solution and we will be able to see this in the figures for hallucinations and, sadly, deaths.  In this area I have no criticism for science, it attempted to use the body’s own defences – what it believed were natural products – to help very sick people.  But it is clearly too simplistic.  Much greater understanding is needed of what is going on.

In the table that follows a list is provided of the drugs and their trade names.

Generic name

Trade name

Interferon alpha 2a

Roferon A

Interferon alpha 2b

Intron A/Reliferon/Uniferon

Human leukocyte Interferon-alpha (HuIFN-alpha-Le)

Multiferon

Interferon beta 1a, liquid form

Rebif

Interferon beta 1a, lyophilized

Avonex

Interferon beta 1a, biogeneric (Iran)

Cinnovex

Interferon beta 1b

Betaseron / Betaferon

Interferon gamma 1b

Actimmune

PEGylated interferon alpha 2a

Pegasys

PEGylated interferon alpha 2a (Egypt)

Reiferon Retard

PEGylated interferon alpha 2b

PegIntron

PEGylated interferon alpha 2b plus ribavirin (Canada)

Pegetron

In June 2016, eHealthme ceased to provide the information on which all the data in this section is based.  On querying my friends in the USA, it would seem that many of the sites that provided similar information, have done the same.  The links we provided to eHealthme also no longer work as this data too has been removed. 

As to why all these sites have removed exceptionally important information, my USA helpers said that more and more people are questioning what they are being given – and demanding to know WHY the CAUSE of their illness has not been investigated.  It appears that there has been a very heartening increase in the numbers of people who want to be healed – have the cause tackled and not the symptoms.  And this is ‘not popular’ with the conventional medical community, who cannot make money from well people.

The statistics collected from eHealthme remain valid for the date they were collected.  As such we have left this section as it is – an historical record.  Please read this section therefore only as an historical record of the figures that were applicable on the date specified.

Side-effects

 

It is very clear from reports of the people who are given the intramuscular injections of IFNs, that the body regards them as toxic.  The most frequent moderate adverse effects are flu-like symptoms: increased body temperature, feeling ill, fatigue, headache, muscle pain, convulsion, dizziness, hair thinning, and depression. But there are some very serious side-effects too.  For example

Hepatitis C virus (HCV) infection affects 2-3% of the population, approximately 170 million people worldwide, causing chronic HCV-related hepatitis with subsequent liver cirrhosis, hepatic failure, hepatocellular cancer, and liver-related mortality in a large number of patients. The gold standard therapy, pegylated interferon alpha in combination with ribavirin can eradicate hepatitis C virus infection in approx. 40% of treatment-naïve patients infected with HCV genotype G1, and only 15-20% of patients with previous treatment. ….. A major barrier to successful treatment is the association of peginterferon/ribavirin therapy with frequent and sometimes serious adverse effects. In clinical trials, approximately 10-15% of treated patients discontinue peginterferon and ribavirin due to adverse events; however, in routine clinical practice, the rate of treatment discontinuation has been reported to be substantially higher. The side effects of peginterferon/ribavirin therapy affect virtually all organ systems, and addition of protease inhibitor can amplify these side effects (particularly anemia), and/or may lead to new ones (i.e., dysgeusia with boceprevir or skin rush with telaprevir). PMID:  22112373

Via the links provided below, you can turn to the eHealthme website where an up-to-date list of side-effects is provided derived form the Adverse Drug Reports submitted by doctors of their patients.  In effect it is a 'real' life list for each drug.  This is an example table for Roferon A

Female Male
Mitral Valve Incompetence Weight Decreased
Retinal Vein Thrombosis Tachycardia Nos
Erysipelas Disease Progression Nos
Blood Pressure Increased Hypophosphataemia
Blindness Unilateral Paranoia
Trisomy 21 Hallucination Nos
Bradycardia Nos Renal Failure Acute
Sinoatrial Block Malnutrition Nos
Syncope Anorexia
Dermatitis Contact Anaemia Nos

 


We present the results of a prospective and a longitudinal study of IFN-beta 1a (Rebif) in the treatment of Mexican patients with relapsing-remittin multiple sclerosis (MS)......Twenty five patients were included ...... Six patients were [then] excluded from the trial, one because of anaphylactic shock, 2 progressed to the chronic form [of MS] and 3 decided not to continue in the study. These patients were considered as treatment failures and represented 24% of the participants entering the trial. The remaining 19 patients ...completed 2-year follow-up.  ....… The most frequent side effects were fatigue, headache, local skin reactions, depressed mood, myalgia, weight variations and somnolence. A few patients developed leukopenia, anemia or elevated liver enzymes. In 31.25% of the patients there was an increase in the number of lesions on MRI, in 31.25% there was a reduction in the number of lesions and in 37.5% no change was noted.

Leukopenia is a decrease in the number of white blood cells (leukocytes) found in the blood, which places individuals at increased risk of infection.   Neutropenia is a sub-type of leukopenia that refers to a decrease in the number of circulating neutrophil granulocytes, the most abundant white blood cells. The terms leukopenia and neutropenia may occasionally be used interchangeably, as the neutrophil count is the most important indicator of infection risk.

Another side-effect of interest to this site, as it is the ultimate spiritual experience, is death.  The following charts again came from eHealthme and were based on the reports from doctors and  SEDA

Avonex - On Jun, 5, 2015: 103,404 people reported to have side effects when taking Avonex. Among them, 2,692 people (2.60%) have Death.

Trend of Death in Avonex reports

Betaseron - On Jun, 2, 2015: 15,006 people reported to have side effects when taking Betaseron. Among them, 622 people (4.15%) have Death.

Trend of Death in Betaseron reports

Pegasys - On Jun, 27, 2015: 18,823 people reported to have side effects when taking Pegasys. Among them, 527 people (2.80%) have Death.

Trend of Death in Pegasys reports

Rebif - On Jun, 1, 2015: 32,038 people reported to have side effects when taking Rebif. Among them, 265 people (0.83%) have Death.

Trend of Death in Rebif reports

 Intron A - On Jun, 27, 2015: 7,494 people reported to have side effects when taking Intron a. Among them, 52 people (0.69%) have Death.

Trend of Death in Intron a reports

 Actimmune - On Jun, 19, 2015: 779 people reported to have side effects when taking Actimmune. Among them, 53 people (6.80%) have Death.

Trend of Death in Actimmune reports

 

 Other products

There are other products that come within this category that have not been investigated in this section, these include the following, the table comes from Wikipedia:

Interferon alfa-2b products
ProductManufacturerFeaturesSpecial uses
Alpharona Pharmaclon    
Intron-A/IntronA Schering-Plough    
Realderon Teva    
Reaferon EC GNC Vector    
Reaferon EC-Lipint Vector-Medica liposomal  
Infagel Vector-Medica ointment  
Recolin Vector-Medica    
Altevir Bioprocess subsidiary liquid, free of HSA  
Viferon Feron suppository or ointment with vitamins C, E viral, bacterial, chlamydiosis
Kipferon Alfarm combination with IgM, IgA, IgG  
Giaferon A/S Vitafarma    
Genferon Biocad    
Grippferon Firn-M nasal formulation influenza
Opthalamoferon Firn-M with dimedrol eye infections
Gerpferon Firn-M with acyclovir, lidocaine ointment herpes

How it works

 

 

Hallucinations can occur through any of the illnesses with which this class of drug is associated via its side-effects.  See the illness section.

 

 

 

References and further reading

  • [Interferon-beta 1a in relapsing-remitting multiple sclerosis. First report of a Mexican population].  [Article in Spanish] - León C, et al Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Insurgentes Sur 3877, Colonia la Fama, CP 14269 Ciudad de México, México.

Observations

The number of hallucinations was correct as of mid 2015.  The figures are derived from the ehealthme website based on the Adverse Drug Reports from doctors.  The link takes you to the up-to-date-page on eHealthme for that drug and its side-effects

 

Observation number

Name of pharmaceutical

No of hallucinations

 016895

Roferon A

 1

 016900

Intron A/Reliferon/Uniferon

 50

 

Multiferon *

 -

 016897

Rebif

 124

 016898

Avonex

 322

 

Cinnovex [same as Avonex]

 -

 016901

Betaseron / Betaferon

 102

 016902

Actimmune

 1

 016896

Pegasys

 91

 

Reiferon Retard [no figures on eHealthme]

 -

016899

Pegintron

 1

 

TOTAL

 692

 

 *Interferon alfa (INN) or HuIFN-alpha-Le, trade name Multiferon, is composed of natural interferon alpha (IFN-α) obtained from the leukocyte fraction of human blood following induction with Sendai virus. The spelling of 'alfa' with 'f' reflects INN naming conventions.  There appear to be no records on eHealthme.

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