Types of human interferon

Interferon in the human body is produced and functions based on the same principles as in other vertebrates. The human IFN system’s peculiarity is the variety of protective and regulatory processes triggered or stimulated by interferon. Depending on which genes encode the form of the IFN molecule, there are 3 types of interferon.

Type I interferons (IFN-1, IFN-I):

  • initiate protective antiviral processes in infected cells and neighboring healthy cells;
  • regulate the strength of the innate immune response (inflammatory response);
  • activate the adaptive immune system and promote the immune memory to protect against re-infection.

IFN-1 is the most studied type of interferon. It includes 16 families. Most of the knowledge is accumulated about the interferon family alpha (IFN-α, IFN-α). IFN-α is most widely used in medicine.

Type II interferons (IFN-2, IFN-II):

  • they stimulate the activity and survival of phagocytes — cells of the immune system that directly fight against foreign particles;
  • they control the development of cells of acquired (adaptive) immunity;
  • they initiate and regulate the antiviral processes of the immune memory during a repeated encounter with an infection.

This type includes only interferon-gamma (IFN-γ).

Type III interferons (IFN-3, IFN-III) are related to type I interferons: they affect the same genes, are involved in the same antiviral and immunomodulatory processes.

This type of interferon was discovered later than the others – in 2003. It is represented by 4 families of lambda interferons (IFN-λ)

Thus, 21 families of human interferons are now known. The duplication of antiviral functions in different families highlights the importance of the interferon system for antiviral protection.

Interferon in medicine

As interferons’ knowledge has increased, scientists have moved from animal studies and cell models to IFN to prevent and treat human diseases. Interferon preparations have shown their effectiveness in viral, oncological diseases and diseases associated with systemic inflammation.

Interferon in acute respiratory viral infections (ARVI)

ARVI accounts for about 83% of human infectious diseases. Perhaps the use of IFN in this area began almost from its discovery and is still developing.

Prevention of ARVI was the first direction in which IFN began to be used in humans. In 1960, 3 years after the discovery of IFN, the English virologist David Tiller injected himself with the drug interferon intranasally (through the nose), and then injected himself with the Coxsackie virus, which causes colds, to understand whether IFN shows preventive properties in humans, and not only on human tissue cells. Together with Tiller, employees of his laboratory voluntarily participated in the experiment. As a result, it was found that the virus was detected in nasal flushes, but the disease developed only in one participant of the experiment is a Tiller himself. Side effects with this method of prevention were absent in all participants.

60 years after the Tiller experiment, in 2020, during the coronavirus pandemic caused by the SARS-CoV-2 coronavirus, interferon preparations were used in different countries worldwide to protect against the pathogen of infection. For example, in the pandemic epicentre, Chinese doctors of Wuhan city used the intranasal drug IFN-α to prevent disease in healthy medical personnel in coronavirus departments. For 28 days of the study, there were no cases. After that, the drug IFN-α was included in the national protocol to prevent coronavirus infection COVID-19.

In Cuba, their colleagues also protected people with weakened immune systems from COVID-19 with the intranasal drug IFN-α. During the 45 days of the study, there were no cases among people undergoing outpatient hemodialysis.

In Russia, the administration of one of the regions distributed free of charge the intranasal drug IFN-α as preventive protection to families where there was at least one sick person. Some Russian companies issued the same drug IFN-α to employees and their family members as part of a kit to prevent coronavirus infection.

Treatment of ARVI is the second important direction of using IFN in humans. This direction also began to develop actively in 2020 during the pandemic, when scientists worldwide urgently grew new drugs to treat a new coronavirus infection or studied the possibility of using existing ones.

Long-term immunological studies of patients with COVID-19 have shown that the coronavirus slows down the active production of IFN for about a week. The most obvious was a review by an international group of scientists from China and the United States that showed that such a delayed response to IFN for a week leads to hyperactivity of the immune system (cytokine storm), damage to vital organs and, in some cases, death.

To compensate for the lack of IFN at the initial stage of the disease, early (within 5 days of the onset of symptoms) treatment with interferon was experimentally tested. Both nebulized (via aerosol) administration of IFN and by injection proved to be effective. Both methods significantly reduced patients’ mortality, severity and sometimes accelerated the recovery process.

Treatment of COVID-19 with IFN is still poorly understood, so IFN drugs have not yet been included in national treatment protocols.

Interferon in herpes

According to the World Health Organization (WHO), about 67% of the world’s population is infected with herpes simplex virus type I (HSV-1) and about 13% – herpes simplex virus type II (HSV-2). The herpes virus is dangerous because it can hide from the human immune system. The disease is amenable only to local treatment for skin manifestations: blisters and ulcers, which contain many new live viruses and are very contagious.

The discovery of IFN has expanded the possibilities for developing more complex drugs for the local treatment of herpes and reducing patients’ infection rate.

As of 2014, the most effective means of treating local manifestations of herpes are combined drugs containing interferon-alpha. Interferon stimulates immune cells to fight more actively against viral particles and infected cells.

Interferon in viral hepatitis B and C

In 2017, WHO Director-General Dr Margaret Chan said: “Viral hepatitis is now recognized as a major public health problem requiring urgent action.” According to the WHO, in 2017, about 5% of the world’s people had viral hepatitis B and C.

The viruses that cause these hepatitis infections affect the liver, and in the chronic form of the disease, lead to loss of liver tissue and death.

Interferons have become the first drugs that have shown their effectiveness for the treatment of viral hepatitis. Active research in this area began in the 70s of the last century. Treatment of viral hepatitis with interferon became widespread in the 80-90s when an industrial technology for producing interferon was developed.

Despite the abundance of side effects with long-term use, interferons have long remained the only available treatment. In 2013, WHO declared interferon-ribavirin combination therapy to be the only commercially available treatment for hepatitis C.

In 2011, a new, safer class of drugs for the treatment of viral hepatitis was registered. Since 2018, WHO has recommended that interferons for the treatment of viral hepatitis should be abandoned, and this new class of direct-acting antiviral drugs should be used.

Development stages of interferon production technology

Leukocyte interferon

The first method of producing interferon was not safe. Interferon was built from donated blood components, taking the disease transmission from the donor to the patient. For example, hepatitis viruses, human immunodeficiency virus, herpesvirus can enter the patient’s body if the blood donor was infected with these viruses.

Most of all, type I interferon can produce immune blood cells-white blood cells. Leukocyte interferon was made from donated blood. First, the white blood cells were filtered out and placed in a nutrient medium in which they could live. Then a harmless virus was injected into the same environment. When the white blood cells detected the virus, they began to synthesize many IFN-I molecules. At the end of the production cycle, the interferon was filtered out and used.

This production method did not allow mass treatment with interferon drugs to begin since the available volumes of donated blood limited it. Scientists were looking for new ways to produce interferon. The development of genetic engineering allowed us to start making interferon on an industrial scale.

Recombinant interferon

In 1973, three American geneticists, Stanley Cohen, Herbert Boyer, and Annie Chang, published details of an experiment about the first successful transfer of fragments of genetic information from one bacterium to another. Thus began the era of genetic engineering. The process of transplanting genes from one DNA to another was called recombination.

In the 80s of the last century, scientists learned to change bacteria’s DNA to produce human interferon. The resulting interferon was safe because it did not contain human blood components. The resulting form of interferon was called recombinant interferon.

As of 2020, this technology is considered the most advanced IFN production technology. It allows the production of recombinant interferon on an industrial scale.

2020: Actual trends in human interferon research

In 2020, current areas of human interferon research were focused on combating the COVID-19 pandemic: