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Role of Cytokines in Schizophrenia

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Introduction:

Schizophrenia is a mental disorder. Over 1% of the world population is affected by this mental disorder (Bakhshi & Chance, 2015). A cytokine hypothesis has been proposed, which elucidates the role of cytokines in this disease. Cytokines such as IL-6, TNF-α, sIL-2R, and IL-1RA were found to be over-expressed by the peripheral blood mononuclear cells (Potvin et al., 2008; Goldsmith et al., 2016), in which interleukin-6 is considered to be the key player in schizophrenia. IL-6 has glycoprotein gp130 as a common membrane receptor and as a signal transducer, which can have both anti-inflammatory and pro-inflammatory effects (Scheller et al., 2011). The anti-inflammatory effects of interleukins present in the blood serum of patients with schizophrenia must be understood. Upcoming therapeutic research focuses on astrocytes due to their expression of class II MHC antigens and the production of pro and anti-inflammatory cytokines. The hypothesized outcome is that IL-6 also induces anti-inflammatory effects which help the astrocytes to maintain the homeostasis. This will enable the researchers to explore further the pathophysiology of schizophrenia based on the cytokine hypothesis. The effects of IL-6 on astrocytes will open the door to a new area of research and will help in exploring the effects.

The impact of the research on Healthcare:

According to the data and statistics from the community studies of the European Union (EU), 27% of the adult population experienced at least one mental disorder in the past year (World Health, 1992). In Ireland, both private healthcare sector and public healthcare sector exists to assist the people of Republic of Ireland during an illness (Book, 2007). The Irish legislation's Health Act 2004 governs the public health care system which is responsible for the people living in Ireland (Pearson et al., 2012). In the year 2010, €2,862 Euros was spent on the health of a single individual residing in Ireland of which 79% was provided by the Irish government (Pearson et al., 2012). Looking the statistics, it is summarized that nearly seven people out of 100 spend the money for treating schizophrenia that would be approximately €20,900 Euros. Biomarkers are biological markers such as viral proteins, cytokine, hormones, etc. which can be used as a measurable indicator of the biological state or condition (O'Connell et al., 2014).  The main challenges in the biomarkers' identification of schizophrenia are the unknown pathophysiology. However, biomarkers such as cytokines are considered due to the development of new hypotheses such as the cytokine hypothesis (Mansur et al., 2012). Understanding the roles of IL-6 in schizophrenia, can be used as a biomarker for the initial clinical diagnosis of schizophrenia patients, and to help create individualized treatment plans.

The timescale for a product launch:

If the research is proven successful, IL-6 based biomarker assays and treatments will be developed as a product from pharmaceutical companies. The developed products such as biomarker assays for IL-6 over or under expression detection and anti-IL-6 drugs will undergo the process of ethical approval and clinical trials which include four major stages. They are pre-clinical trials, clinical trials (Phase I, II and III), ethical approval and marketing (Phase IV) which would take a period of 20 to 30 years (DiMasi et al., 2003). There are anti-IL-6 drugs already in the market for the treatment of diseases which are related to Auto-immunity and other immune-based diseases which can cross the blood-brain barrier. These drugs may take a period of 8 -15 years to is the anticipated timescale for the proposed benefits to come into the market for the utilization of the schizophrenia patients.

The importance of the product:

The anti-inflammatory effects of IL-6 occur due to classical signaling pathway in which IL-6 binds to the membrane-bound cell surface receptor (IL-6R). Trans-signaling pathway provides the pro-inflammatory implications of the IL-6 (Scheller et al., 2011). Blocking the Trans-signaling pathway of the IL-6 is the target for the anti-IL-6 drugs. This might hold the capabilities for the treatment of Schizophrenia. The biomarker assays for IL-6 detection may help a person to identify whether the person is susceptive to schizophrenia shortly. This can help the doctor to give personalized treatment for the person based on the medical technologies available.

The importance of the IL-6 product can be understood from the article "Young people have the highest rate of psychiatric admissions" which was published in Irish Times on 21 July 2016. The article discussed the young people (20 to 24) who are getting admitted to psychiatric hospitals for the 2015 (Edwards, 2016). The major diseases diagnosed for the admission are schizophrenia, depression, alcoholic disorders and mania which increases day by day (Edwards, 2016).

Correlation with public, governmental and business sectors

Public awareness campaigns and outreach to the doctors is the primary step in spreading the importance of the "IL-6 as a biomarker for schizophrenia" research. The second phase would be to use the primary media tools such as newspaper and radios so that the people does not expect from the research or get panic or distressed by the research. If the product is ethically permitted and the research becomes a success a contract between a pharmaceutical company or a medical diagnostic device company for establishing the result in the society.

The completed biomarker assays for IL-6 detection product would be straightforward and easy to use similar to us such as a blood sugar and cholesterol test which can be utilized by the public without the doctor's supervision. Biomarker assay kinds of products are advertised in the media such as television, newspaper, the internet, etc. for the maximum dissemination of the product. In the case of anti-IL-6 drugs, a patent is claimed by the pharma company which owns the contract, and a certain amount of percentage is given as royalty to the researcher. The patent is registered in a common government body, and the prize is sometimes fixed by the government of the country which accepts the drug.

Conclusion:

Schizophrenia is perhaps the most daunting psychiatric disorder, characterized by its life-altering symptoms, such as hallucinations and delusions. There is currently no precise explanation of its pathophysiology. Schizophrenia is explained as the biochemical imbalance in the brain which may exist due to many factors. Upcoming therapeutic research focuses on astrocytes due to its expression of class II MHC antigens and the production of pro and anti-inflammatory cytokines. By combining the Cytokine hypothesis and Neurodevelopmental hypothesis, it is possible to understand the pathophysiology of schizophrenia and the role of astrocytes in maintaining the homeostasis and cytoarchitecture of the brain. The cytokine IL-6 has been regarded as a pro-inflammatory cytokine, but it also has many anti-inflammatory and regenerative activities. Understanding the roles of IL-6 in schizophrenia can be used for the initial clinical diagnosis of schizophrenia patients, and to help create individualized treatment plans. Products such as biomarker assays for IL-6 and anti-IL-6 drugs can be developed for the treatment of schizophrenia from the research. The anticipated timescale for these drugs or assays to come into the market can take a period of 8 -15 years. A decade is not a big issue for the young people who are getting admitted to psychiatric hospitals diagnosed a schizophrenic patient. This can help the doctor to give personalized treatment for the person based on the medical technologies available.

References:

Bakhshi, K. & Chance, S.A. (2015) The neuropathology of schizophrenia: A selective review of past studies and emerging themes in brain structure and cytoarchitecture. Neuroscience, 303, 82-102.

Book, I.S. (2007) Irish Statute Book.

DiMasi, J.A., Hansen, R.W. & Grabowski, H.G. (2003) The price of innovation: new estimates of drug development costs. Journal of health economics, 22, 151-185.

Edwards, E. (2016) Young people have highest rate of psychiatric admissions. In Secondary Edwards, E. (ed) Secondary Young people have highest rate of psychiatric admissions, pp. Pages, http://www.irishtimes.com/news/health/young-people-have-highest-rate-of-psychiatric-admissions-1.2729673 (February 24, 2017).

Goldsmith, D.R., Rapaport, M.H. & Miller, B.J. (2016) A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry, 21, 1696-1709.

Mansur, R.B., Zugman, A., Asevedo, E.M., da Cunha, G.R., Bressan, R.A. & Brietzke, E. (2012) Cytokines in schizophrenia: possible role of anti-inflammatory medications in clinical and preclinical stages. Psychiatry Clin Neurosci, 66, 247-260.

O'Connell, K.E., Thakore, J. & Dev, K.K. (2014) Pro-inflammatory cytokine levels are raised in female schizophrenia patients treated with clozapine. Schizophr Res, 156, 1-8.

Pearson, M., Lafortune, G. & Vincent, F. (2012) Health spending in Europe falls for the first time in decades. In Secondary Pearson, M., Lafortune, G. & Vincent, F. (eds) Secondary Health spending in Europe falls for the first time in decades, pp. Pages, http://www.oecd.org/newsroom/healthspendingineuropefallsforthefirsttimeindecades.htm (February 24, 2017).

Potvin, S., Stip, E., Sepehry, A.A., Gendron, A., Bah, R. & Kouassi, E. (2008) Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry, 63, 801-808.

Scheller, J., Chalaris, A., Schmidt-Arras, D. & Rose-John, S. (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta, 1813, 878-888.

World Health, O. (1992) The ICD-10 classification of mental and behavioural disorders : clinical descriptions and diagnostic guidelines. World Health Organization, Geneva.


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