Interferons: a viable alternative to antibiotics?
Interferons: a viable alternative to antibiotics?
Richard S Müller
Consultant
As we all know the macrophage plays an essential role in initiation and maintenance of the immune response, and so in light of the increased incidence of antibiotic resistance, this article looks at the use of interferon treatments as an alternative to the use of antibiotics as a first line treatment.
Interferons are immunomodulatory molecules that show a wide range of applications due to their antiviral, antibacterial, antitumour and inflammatory activities. Whilst recombinant and natural interferons are among the most common biological therapeutics worldwide, interferon inducers are hardly mentioned in the West. With the increase in antibiotic resistance, is it time to revisit this alternative class of medications?
When interferon treatment was being developed in the Soviet Union, this was effectively overlooked in the West during the cold-war era due to its concentration on the development of vaccines. These days, antibiotics are the standard route of treatment in the West with no mention of any use of an alternative method of treatment, and no active development of interferon treatments for this purpose by Western pharmaceutical companies.
"When interferon treatment was being developed in the Soviet Union, this was effectively overlooked in the West..."
Today, it is only in the Russian Federation and a handful of other countries (where they represent a substantial market share of modern pharmacopoeia) that the possibility of treatment with interferon is an option.
Infection challenges in the West
Despite the broad range of both inactivated and live vaccines developed in recent years, influenza prevention remains an urgent problem. In earlier years, the absence of 95% effectiveness of vaccine administration was attributed to either improper methods of vaccine storage or transport, or a deficiency in the immunogenic capability of the preparations used. At the present time, one of the largest factors contributing to a patient’s failure to seroconvert, or to an insufficient period of time for antibody production, is an inability of the patient’s own immune system to respond adequately to the vaccination1,2.
It is well known that in the elderly (a growing group in our ageing population) anti-viral vaccines accomplish seroconversion much less frequently than in healthy younger individuals. Age-related immunodeficits are associated with the shrinking of the thymus, which results in a decrease of thymus-dependent humoral immunity and a simultaneous increase in the concentration of immunoglobulins, especially IgA and IgG, with a predominance of ‘less-effective’ antibodies3.
There are various reasons cited for the increase in antibiotic resistance, but the most commonly cited reasons can be divided into a few groups:
1) Use of an inappropriate ‘cheap’ antibiotics
2) Use of an inappropriate dosage
3) Use of an inappropriate duration of treatment
4) Failure to utilise the option of the newer fluoroquinalones
Looking at these reasons, we often see cost pressures in the NHS leading to the prescribing of the cheapest antibiotic available without any clinical tests and then a step up approach to the second cheapest antibiotic, and so forth. In other foreign countries, for example in the former Soviet Union, a speedy lab test of a sample provides the clinician with a definitive guide to the causative organism. This identifies the most effective treatment and inappropriate antibiotic use is restricted through use of the most appropriate one, or indeed none at all.
"...in the former Soviet Union, a speedy lab test of a sample provides the clinician with a definitive guide to the causative organism."
There have also been regular cases of an inappropriate dose being prescribed by a clinician off the licensed dose. Consider the example when Amoxicillin is prescribed to children with recurrent otitis media (middle ear infection). Whilst a clinician will often prescribe the standard children's dosage of 125 mg three times daily, closer inspection of the Summary of Product Characteristics (SmPC) will show that this dose should be increased for more recurrent infections. An extract from the SmPC for GlaxoSmithKline’s Amoxil Paediatric Suspension states "In severe or recurrent acute otitis media, especially where compliance may be a problem, 750 mg twice a day for two days may be used as an alternative course of treatment in children aged 3 to 10 years". However, it is arguable that in many cases of recurrent infection the increased dose is not routinely prescribed.
Where the licensed duration of an antibiotic is not for a fixed period, but a variable period such as 7 to 14 days, there is often the temptation for the clinician to prescribe at the lowest duration or indeed for the patient to terminate their treatment at the end of the shorter period had they been prescribed a longer duration course.
There is some evidence that the appropriate use of certain newer quinalones, such as moxifloxacin (a fluoroquinalone from Bayer), for certain respiratory conditions (such as chronic obstructive pulmonary disorder) can reduce the number of exacerbations and consequently reduce the amount and frequency of antibiotic use. However, cost pressures and prescribing guidelines actively dissuade clinicians from the use of these more highly effective treatments.
Potential role of interferons
The question of using interferons as immunomodulators not only for the treatment of immunodeficient conditions, but also in prevention of infectious diseases, should be discussed.
Administration of interferons has shown promise in the prevention of polyetiologic diseases, such as respiratory illness, against which effective means of prophylaxis (vaccine) has been inadequately developed. This was confirmed by T. A. Semenenko under controlled epidemiological experiments, which demonstrated interferons’ effectiveness as a non-specific preventive drug against infectious disease4, 5.
There is also evidence of the possibility of using interferons to increase the human organism’s resistance and for stimulating adequate reactivity when various vaccines are introduced into the body6, 7, 8.
One of the preparations to show promise in recent years is the interferon inductor "Arbidol", created by the Center for Chemical Medicines at the Chemical-Pharmaceutical Scientific Research Institute of Russia. This drug has been approved by the Russian Federation Ministry of Health for clinical use in adults9. Arbidol has a wide spectrum antiviral effect upon RNA and DNA-containing viruses. The preventive strength of the drug against influenza and RSV has been confirmed in both adult and child populations10, 11.
It can also be noted that in addition to the effective use of macrophage treatments with interferon inductors in monotherapy as an alternative to antibiotics, there is some evidence to show the synergistic use of the two forms of treatment combined in poly-pharmacy.
"Should an interferon alternative be introduced, or used to augment existing treatments?"
Macrophage stimulation or activation can be initiated by a variety of different stimuli including beta-glucans (such as Beta-1,3-D glucan) which are orally effective, non-toxic and a very powerful stimulator of the immune response. Consequently, interferon inductors can be used in conjunction with beta-glucans for an increased response in those population groups typically less responsive to traditional medication such as the elderly, and arguably those with respiratory problems
Interferon inductors present an opportunity to intervene at the level of host-pathogen interface, a therapeutic tool for emerging infections, especially when conventional treatment with antibiotics is ineffective due to antibiotic resistance or inavailability (rapidly spreading, endemic).
Conclusion
With the growth in noscomial infection and the possibility of the transfer of resistance between secondary and primary care, should we radically rethink our use of antibiotics?
Should an interferon alternative be introduced, or used to augment existing treatments?
Should we test more, so we prescribe less?
References:
1) Nacharova Ye. P., Kharit S. M., Petlenko S. V. Preventive immunocorrections as a method of increasing the safety and effectiveness of vaccination. Terra Medica. 2004, 1 (33): 3-7.
2) Orlova T. V., Sykhovei Yu. G., Unger I. G. The dependence of preventive influenza vaccine effectiveness on the initial condition of the immune system. Epidemiology Vaccineprof. 2004, 4 (17): 17-20.
3) Yerofeeva M. K., Paramonova M. S., Maksakova V. L. et al. On the tactics of influenza prevention in the elderly. Journal of Microbiology. 2001, 3: 91-93.
4) Semenenko T. A. Epidemiological foundations for administration of immunomodulators for the prevention of infectious diseases. MD Auto. Dissertation. M., 1989.
5) Semenenko T. A. Epidemiological aspects of nonspecific prophylaxis of infectious diseases. Vestn. Russian Academy of Medical Science News. 2001, 11: 25-29.
6) Yerofeeva M. K. The prophylaxis of influenza and RSV in risk groups. MD Auto. Dissertation. 2001.
7) Kiselev O. I., Marinich I. G., Sominina A. A. Influenza and other respiratory viral infections. S.P.B. 2003.
8) Nacharova Ye. P., Kharit S. M., Petlenko S. V. Preventive immunocorrections as a method of increasing the safety and effectiveness of vaccination. Terra Medica. 2004, 1 (33): 3-7.
9) Glushkov R. G., Guskova T. A., Krylova L.Yu. et al. The mechanism of arbidol’s immunomodulating action. Vestn. Russian Academy of Medical Science News. 1999, 3: 36-40.
10) Uchaikin V. F., Shuster A. M., Kladova O. V. et al. Arbidol in the prevention and treatment of influenza and other acute respiratory infections in children. Pediatria. 2002, 6: 1-4.
11) Shumilov V. I., Shuster A. M., Lobastov S. P. et al. The effectiveness of arbidol in the prevention and treatment of acute respiratory infections among military servicemen. Voen.-Med. Zhur. (Military Med. Journal). 2001, 323 (3): 51-53.
About the author:
Richard Müller is an independent consultant working in various countries in the pharmaceutical, medical devices and biotech field, and holds Clinical Diplomas in Cancer, Coronary Heart Disease, Diabetes and Mental Health. He is an Affiliate Member of the Royal College of Paediatrics &, Child Health, Associate Member of the Royal Society of Medicine and the Royal Society for Public Health, Member of the Institute of Health Promotion &, Education and a Fellow of the Royal Society of Tropical Medicine and Hygiene. He can be contacted by email on muller@tesco.net.
Should the West be using interferons more and antibiotics less?
