Introduction

Interferon therapy refers to the clinical practice of using interferons to treat diseases. Interferons are a family of naturally occurring signalling proteins that are released by your body’s cells.¹ These include the white blood cells (lymphocytes) that make up the immune system. The release of interferons serves to prime the body's response to viral infections. Interferons also form part of the body's arsenal for fighting non-infective diseases such as cancer. Interferons are a part of the innate immune system which is the first line of defence against illnesses.¹

Due to their native roles in alleviating disease in the human body, interferons have been adopted exogenously for use in the treatment of various medical conditions. Diseases that can be treated with interferons include viral infections such as hepatitis (hepatitis C), some types of cancers as well as auto-immune disorders.¹ Researchers are looking into the prospects of developing interferons for treating other diseases such as asthma.²

In this article, you will gain some insights into how asthma develops, and how interferons could potentially serve as a remedy to attenuate the inflammatory pathways involved.

Brief description of interferons

Classification of interferons

3 main groups of interferons fall under 2 Types, Types 1 and 2. These are Interferon alpha (IFN-α), Interferon beta (IFN-β), and Interferon gamma (IFN-Ɣ). IFN-α and IFN-β fall under Type 1 whilst IFN-Ɣ falls under Type 2. Recently, a fourth group of interferons has been identified. They are referred to as Interferon lambda (IFN-ƛ) which has been assigned to Type 3.^1,3

How interferons work

Interferons, once released by virus-infected cells, attach to specific proteins referred to as receptors on the surfaces of lymphocytes. The binding of interferons to the receptors of lymphocytes elicits a cascading chain of events that leads to the release of antiviral proteins that will fight the infection.³

How interferons are used in medicine

In the treatment of diseases, interferons are introduced into the body through subcutaneous or intramuscular injections. IFN-α, in conjunction with ribavirin, is used to treat viral hepatitis C.⁴ IFN-α is also administered to treat cancers eg. non-Hodgkin lymphoma, hairy cell leukaemia, multiple myeloma, and renal cell carcinoma. 

IFN-β, subgroups 1a and 1b, is indicated for the treatment of multiple sclerosis whilst IFN-Ɣ is administered for treating chronic granulomatous disease.¹

Asthma

Defining the disease

Asthma, is a chronic respiratory disease that is characterised by episodes of inflammation and the narrowing of the airways of the lungs. The consequence of airway constriction is difficulty in breathing as air passage becomes restricted. 

Asthma may develop at any age but typically starts in childhood as paediatric asthma. This condition is one of the most common non-communicable diseases globally, being the most prevalent chronic condition in children. It affects more than 200 million people globally, with over 400,000 associated deaths having been reported for 2019.

There are numerous triggers of asthma attacks. These include allergies, the weather, or even stress. Asthma attacks may also be exercise-induced. Asthma is therefore typically defined as being allergic (type 2 asthma) or non-allergic, but there is a growing body of evidence that there could be other types of asthma. In some cases asthma co-occurs with chronic obstructive pulmonary disease (COPD) in a disease state termed asthma-COPD overlap syndrome (ACOS).⁵ COPD is also a respiratory disease.

Despite asthma being a lifelong and incurable pulmonary condition, there are available treatment and management options that can ensure a normal, healthy, and long life. This is evidenced by the fact that some elite athletes are living with the condition.⁶ Even though asthma is treatable and manageable, some health complications are associated with asthma. Asthma is typically characterised by intermittent attacks void of any symptoms in between, but the disease may also be persistent.

Symptoms

• Chest pain and tightness
• Breathlessness
• Coughing and wheezing
• Increased heart rate
• Blueness of the lips and fingers
• Disorientation, dizziness and drowsiness
• Fainting
• Increased heart rate

Health complications associated with asthma

If not treated and controlled properly, asthma may lead to several long-term or irreversible complications. Asthma attacks may also be fatal if not treated or attended to timeously. These are some of the asthma-related complications:

• Constant fatigue that may lead to underperformance at school or work
• Childhood asthma may lead to underdevelopment
• Infections⁷
• Asthma patients are more prone to pregnancy-related complications such as preeclampsia
• Nighttime wheezing, coughing, and shortness of breath may disrupt sleep
• Emphysema whereby the alveoli (air sacs) in the lungs become damaged to such an extent that they start merging to form cocoons⁹

Risk factors

Numerous risk factors are associated with developing asthma. These include environmental conditions as well as genetics.¹⁰ Some of these factors are triggers of episodes in sufferers. 

• Genetics. You are more likely to develop asthma if close family members are sufferers of the condition
• Smoking increases your chances of developing asthma and other pulmonary conditions
• Obesity 
• Pollution factors such as contaminated air
• Stress
• Allergies
• Infections such as pneumonia

Existing asthma treatment options 

Treatment and management of asthma as well as the side effects associated with the current drugs

There is a plethora of pharmaceuticals that are indicated for the treatment and control of asthma. Several classes of drugs are administered for the treatment and prevention of asthma attacks (Table 1). There are several steps in the treatment of asthma, based on the severity or progression of the attack:^11,12

1. Short-acting beta-2 agonist and low-dose inhaled corticosteroid for intermittent attacks
2. For persistent mild asthma, a low-dose inhaled corticosteroid daily in conjunction with a short-acting beta-2 agonist
3. For persistent moderate asthma, a low-dose inhaled corticosteroid in conjunction with a long-acting beta-2 agonist. A low-dose inhaled corticosteroid can also be used in conjunction with a long-acting beta-2 agonist, or a leukotriene receptor antagonist or a xanthine
4. Medium dose inhaled corticosteroid daily in combination with a long-acting beta-2 agonist. The medium-dose inhaled corticosteroids could also be administered in combination with a xanthine or a leukotriene receptor agonist. This step is included as an additional measure to treat persistent moderate asthma
5. For severe persistent asthma, a daily medium/high dose of inhaled corticosteroids may be administered in combination with a long-acting beta-2 agonist and an anticholinergic. Immunomodulatory drugs may also be administered for severe persistent asthma
6. As an additional measure to treating severe persistent asthma, a daily high-dose inhaled corticosteroid and a long-acting beta-2 agonist may be administered. Immunomodulators may also be applied in this step

Table 1: Classes of drugs used to treat asthma and some of their side effects.¹³

Inflammatory elements involved in asthma pathology

The pathology of asthma is attributed to lymphocytes referred to as the T helper cells (Th cells), more especially the T helper 2 (Th2) cells. The Th2 cells release interleukins which are major factors in the inflammatory responses observed in asthma patients. This inflammatory response is also launched by the antibody Immunoglobulin E (IgE). IgE recruits various lymphocytes to the airways whereby they promote the inflammation that leads to asthma attacks.¹⁴

Underlying principles in interferon therapy for asthma

Role of interferons in modulating immune responses in asthma

Type 1 interferons hinder the development and functioning of Th2 lymphocytes by preventing the release of the interleukins that are implicated in asthma development. Type 3 interferons, on the other hand, interact with other types of lymphocytes to decrease their proinflammatory activities. Furthermore, inefficiencies in Type 1 interferons may lead to severe asthma.^15,16

The balance of T helper cells in asthma pathology and how interferons could be a solution

For asthma pathology, it is thought that the activity of Th2 lymphocytes relative to the activity of T helper 1 cells (Th1) is responsible for the observed inflammation. In asthma patients, the scale is tipped towards Th2 lymphocytes whereby Th1 lymphocytes are less active. The resultant condition is that the Th2 lymphocyte pathway is favoured to result in the proinflammatory state that is associated with asthma. This is because Th1 and Th2 lymphocytes are supposed to balance each other out so that no one pathway prevails over the other.¹⁴ 

Therefore, the concept of administering interferons in asthma patients is premised upon the fact that Type 1 and Type 3 interferons inhibit Th2 lymphocytes and their proinflammatory pathways. 

To this effect, the administration of interferon therapy has been shown to have the potential to reduce asthma-related inflammation in numerous studies. Preclinical studies with mice showed that interferons result in reduced asthma symptoms. Clinical trials with asthma patients have also shown the potential of interferon therapy in treating the condition.¹⁵

Known side effects of interferon therapy

Interferon therapy is accompanied by numerous side effects, some of which are severe. These should be taken into consideration when developing interferons as therapeutics for asthma.¹

• Psychiatric disorders such as disorientation, poor concentration, depression, and manic episodes ^17,18
• Flu-like symptoms such as fever, nausea and vomiting
• Increased susceptibility to infections
• Hair loss or thinning

Summary

Interferon therapy entails the use of interferons as drugs to treat various diseases. The diseases include viral infections, autoimmune disorders, and some types of cancer. 

Interferons are naturally occurring signalling molecules of the innate immune system which have been exogenously modified and adapted for medicinal use. Since interferons also interfere with the inflammatory pathways, they are being developed for the treatment of asthma. 

Asthma is an inflammatory disease that results in swelling and narrowing of the airways in the lungs. Interferon therapy is believed to have the potential to modulate the immune system to treat asthma, inducing inflammation. 

The potential of interferon therapy in treating asthma has been showcased from the preclinical and clinical studies conducted. In developing interferons as therapeutic drugs for treating asthma, considerations should be made around the subject of the side effects of interferons. This is because some side effects of interferon therapy are quite serious.