What is the INF-y cytokine?
Cytokines are the unsung heroes of the immune system, often acting as the first responders to a pathogen infection.
IFN-γ increases the efficiency of immune system by enhancing its competence to deliver anti-microbial effector functions.
What happens when we produce too much ?
Over-activity of IFN-γ has been reported to cause excessive tissue damage, necrosis and inflammation and may contribute to disease pathology.
Hyper-activity of both IFN-γ and IL-18 can exacerbate pathogenesis in Burkholderia infections. Irregular production of IFN-γ has been linked with autoimmunity and alterations in gut flora. Therefore, IFN-γ activity is a double edged sword and immune regulatory mechanisms strive to strike a delicate balance between infection control and disease pathology in this regard
A complex interplay between immune cell activity and IFN-γ through coordinated integration of signals from other pathways involving cytokines and Pattern Recognition Receptors (PRRs) such as Interleukin (IL)-4, TNF-α, Lipopolysaccharide (LPS), Type-I Interferons (IFNS) etc. leads to initiation of a cascade of pro-inflammatory responses.
The therapeutic potential of IFN-γ can be limited owing to huge cost of treatments and side effects such as flu, lethargy, suppressed nervous system, cough etc.
Although these accompanied adverse effects do minimize the efficacy and potential of such immunomodulatory
therapies, IFN-γ administration still proves to be beneficial and an effective adjunct to the existing drug regimen in this era of rapid and formidable drug resistance.
Thus, cytokine intervention can control several of the life-threatening and debilitating infections. Targeting IFN-γ has been seen as a new therapeutic approach for combating atherosclerosis, as it is reported to be key player involved in the development and disease manifestation of
atherosclerosis.
Clinical investigations have further substantiated the role of IFN-γ in progression of cardiac diseases.
Patients suffering from chronic heart failure reported to have a higher serum IFN-γ levels as compared to healthy controls.
Moreover, myocardial tissues of patients suffering from Chagas’ cardiomyopathy displayed significant up regulation of IFN-γ-inducible genes, suggesting a direct link of IFN-γ signaling in this parasite-induced heart problem. Individuals with peripartum cardiomyopathy upon treatment with ACE-inhibitors, beta-blockers and diuretics resulted in improved cardiac function along with lowering down of serum IFN-γ levels
which was high otherwise. Additionally, levels of IFN-γ in serum and cerebrospinal fluid have also been found up-regulated in the neurodegenerative disease, Amyotrophic lateral sclerosis (ALS).
Hence, linking this key pro -inflammatory cytokine with the progression of the disease. Elevated levels of serum IFN-γ has also been reported in patients with Parkinson’s disease.
Source: Published Medical Journal https://www.degruyter.com/document/doi/10.1515/bmc-2018-0007/html
How is this relevant to the Pfizer COVID-19 Vaccine
IFN-y in non-human studies
IFN-y in phase 1 Trial
The interferon-gamma pro-inflammatory cytokine is up-regulated at a far greater level than Interleukin cytokines.
This may result in imbalance of immune homeostasis, increased inflammation, and increased disease incidence.