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REVIEW ARTICLE
Year : 2020  |  Volume : 34  |  Issue : 2  |  Page : 57-62

Interleukin types and its application


Department of Biotechnology, R.V. College of Engineering, Bengaluru, Karnataka, India

Date of Submission07-Apr-2020
Date of Acceptance10-Jun-2020
Date of Web Publication20-Nov-2020

Correspondence Address:
Dr. Praveen Kumar Gupta
Department of Biotechnology, R.V. College of Engineering, Bengaluru - 560 059, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijaai.ijaai_11_20

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  Abstract 


Interleukins (ILs) were the first expressed by leukocytes that aid in the communication between cells. There have been extensive studies on various types of IL, and it was found that they help in motility, cell growth, and differentiation. They have been grouped into four major groups based upon their structural features. This article explores the characteristics of various IL where studies on each type and its associated autoimmune diseases have been reviewed. This article also highlights on the recent advances and applications in the field.

Keywords: Autoimmune diseases, cytokines, immunology, inflammation, interleukins


How to cite this article:
Arokiaraj J, Mugunthan A, Gupta PK. Interleukin types and its application. Indian J Allergy Asthma Immunol 2020;34:57-62

How to cite this URL:
Arokiaraj J, Mugunthan A, Gupta PK. Interleukin types and its application. Indian J Allergy Asthma Immunol [serial online] 2020 [cited 2020 Nov 26];34:57-62. Available from: https://www.ijaai.in/text.asp?2020/34/2/57/300914




  Introduction Top


Interleukins (ILs) were found to be expressed by leukocytes and mediate communication between the cells. Their major role is to create a stimulus for immune responses such as inflammatory conditions.[1]

Cytokines are usually <80 kDa in size and are classified as signaling proteins. The first group of cytokines were known as immune response factors and labeled as lymphokines. These were released from activated lymphocytes in response to polyclonal antigen. They have a broad range of biological functions and are involved in cell interactions and are secreted by many cell types at high concentrations. Therefore, they have an effect on adjacent cells and thus function in a paracrine fashion. They also cause systemic or endocrine effect and in turn have effects on the cell origin.[2]

Furthermore, cytokines have been effective adjuvant molecules where they induce delayed hypersensitivity. Some of which are IL-6 and IL-8.[3]

IL and the immune system are greatly correlated using rare deficiencies. These mostly include autoimmune diseases such as psoriasis, arthritis, dermatitis, sepsis. Synthesis of ILs occur mainly from helper cluster of differentiation (CD4) T-lymphocytes, monocytes, endothelial cells, and macrophages and aid not only in the development but also in the differentiation of T, B hematopoietic cells, and lymphocytes.[4]

IL receptors in the hippocampus are responsible for developing spatial memories in mice. They are grouped accordingly based on the sequence homology similarities in the receptor chains. All immune cells have different functional properties which are based on their respective surface receptors, such as CD4, CD8 T-cells, and B-cells. Research has found that immune and inflammatory responses cause the growth of ILs to increase. The interactions with various types of cell result in the suppressive and effective roles.[5]

There are various types of IL that have been labeled, but only to a certain extent, the immunological functions are known for most. IL-1 and IL-2 have major roles such as activation of lymphocytes, where IL-2 helps in the growth of T- and B-cells. Furthermore, IL-1 and IL-6 are the mediators of inflammation. T- and B-lymphocytes are primarily activated by IL-1 and IL-2 where it helps in cell maturation and IL-4 increases the secretion of antibodies through B lymphocytes, whereas IL-12 causes an increased production of the leukocytes, cytotoxic T-cells, and natural-killer (NK) cells. The ILs secreted due to the specific stimuli will help determine some of the clinical diseases and manifestations that are associated.[6]


  Mechanism Top


As shown in [Figure 1], ILs are unlike other cytokines, thus are secreted only when a stimulus is released from an infectious agent. When an IL is stimulated, it binds to the receptor and in return it causes a cascade of events by sending the signals to the target cell, thereby altering the behavioral characteristics of the cell. At first, ILs were only thought to act as modulators, but now we know that they interact and are responsible for a broad range of physiological functions.[3],[7]
Figure 1: Mechanism

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  Significance Top


Interleukin-1

IL-1 has a major role in affecting all tissue and organs in the system. It is also known to be as the pro-inflammatory cytokine as it expresses a wide range of protein synthesis and genes. This causes an induced chronic and acute inflammatory change in the system. Since this is known as the “alarm” cytokine, it brings about a range of defense mechanisms. The disadvantage of overproduction of IL-1 leads to the debilitation of host functions. Thus, the reduction of synthesis of IL-1 has become a target in the therapy of various diseases.[8]

Interleukin-2

IL-2 is used for treating metastatic melanoma and renal cell carcinoma as its regarded as a good immunotherapeutic agent. Even though high dosage of IL2 has clinical benefits, it is limited in broader groups in the clinical use. However, low dosage of IL-2 has resulted in disappointing response in the treatment of melanoma. However, in the case of renal cell carcinoma, the response rates have been slightly better. Thus, the response rates have been 60% when IL-2 is added with chemotherapeutic agents to patients suffering from metastatic melanoma. However, this has not contributed in any way for improved survival rates. It is still under determination if addition of new agents along with IL-2 will provide better response.[9],[10] According to [Figure 2], T Helper cells and Natural killer cells help in the production of B cells, Macrophages, Natural killer cells and activated T cells.[10],[11]
Figure 2: Interleukin 2

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Figure 3: Interleukin 10 and 12

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Interleukin-6

IL-6 has a major role in regulating the regulatory responses. It binds to the receptor and leads in signal transduction through different pathways such as Janus kinase, mitogen activated kinase, and phosphatidylinositol 3′ kinase. These pathways contribute in the various ways such as migration and tumor cells invasion. The expression of IL-6 in different types of cancer have led to metastasis. However, blockage of IL-6 has displayed its therapeutic role by improving the symptoms in Castleman's disease and rheumatoid arthritis.[12]

Interleukin-10

Interleukin-10 IL-10 acts as an immunoregulatory cytokine. It is responsible for the proliferation of several immune cells. In recent studies, it has been shown that it has immunestimulatory functions that causes limited inflammation by eradicating infectious or noninfectious agents. However, increased expression of IL-10 was found in lymphomas and melanoma and thus concluded to promote further tumor development.[10],[13]

Interleukin-12

IL-12 is known to be a heterodimeric cytokine that is being produced by Langerhans cells and phagocytic cells. The production is, however, induced by fungi, bacteria, and viruses and mediated through CD40 ligand interaction. IL-12 is regulated by feedback mechanisms such as positive and negative. During the T-cell expansion if both IL-12 and its induced interferon are present, Thelper cells of Type 1 is generated, whereas Type 2 is inhibited. The inhibition of Thelper cells of Type 2 has a suppressive response to allergic reactions. While the Type 1 cells are responsible for autoimmune diseases. Thus, this particular IL is undergoing clinical trials in HIV and cancer patients, as it has a powerful in vivo antitumor effect.[10],[11]

Interleukin-16

Interleukin-16 IL-16 is also known as lymphocyte chemo- attractant factor, which is chemotactic to immune cells such as monocytes, eosinophils, T-cells. IL-16 is increased in production during allergic responses. It is especially produced in the bronchoalveolar fluid and nasal tissue of asthma patients. Thus, IL-16 activates the eosinophils to activate the response to allergy.[14],[15]

Interleukin-17

Recent studies have displayed a huge importance of IL-17 in the pathogenesis of psoriasis as shown in [Table 1]. Thus, this has provided a new target for biological therapy. The US Food and Drug Administration has agreed to the anti IL-17 agent, which is a medication found to be promising for the patients suffering from moderate to severe plaque psoriasis. This has been confirmed by the efficacy of monoclonal antibodies blocking IL 17A, such as secukinumab and ixekizumab. Brodalumab (siliq) has also been recently given approval for treating plague psoriasis in adults whose phototherapy have not been successful.[16],[17],[18]
Table 1: Types of Interleukins

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Interleukin-18

IL-18 has a major role in Th1 response, and it also is an Interferon gamma inducing factor. This may be the reason for sarcoidosis progression. Sarcoidosis disease is known to be multisystemic and is characterized due to the formation of granulomas as shown in [Table 1].[19],[20]

Interleukin-30

Prostate cancer is highly associated with IL-30 as it supports in vitro tumor growth. As in recent studies, metastatic prostate cancer is the main cause that leads to death in men globally. Thus various therapeutic approaches may be undertaken for cancer progression.[21]

Interleukin-33

IL-33 belongs to the IL-1 family and is one of the recent discovery. When IL-33 is bound to receptor, it exerts particular functions such as pro-inflammatory functions by inducing Type 2 cytokines. Disruption of receptor signals enhances the anti-tumor response in murine breast carcinoma. It has been detected that the expression of IL-33 was found to be in the serum of breast cancer (BC) patients. By using immunohistochemistry methods, the percentage of IL-33 was found to be twice as much in BC patients than patients with benign breast disease. Thus, IL-33 has a role in BC progression and is used as a biomarker for metastasis of BC. Under pathophysiological situations, IL-33 causes the activation of NK and T-cells.[22]


  Future Perspectives Top


Novartis

Novartis is a Swiss pharmaceutical company based in Switzerland. It is the largest company in both market capitalization and sales. It conducted some studies on canakinumab (ACZ885) which reduces the cardiovascular risks by targeting IL-1.[23]

Eli Lilly

Eli Lilly acquired autoimmune drug rights by paying Nektar $150M up front. The Nektar drug can be easily used by the patients by injecting themselves one to two times a month. This drug is to be later tested on patients with autoimmune diseases such as psoriasis. natural-killer tumor recognition-358 helps in targeting the imbalance in various immune cells that is caused by many autoimmune conditions. The blockage of IL-2 will cause the production of inhibitory immune cells.[24]

Novo Nordisk

Novo Nordisk is a leading company in diabetic care and is an expert in the areas of homeostasis management and hormone replacement therapy. This company has licensed IL-21 monoclonal antibody and patent rights to IL-21 antibodies. Novo Nordisk is undertaking tasks to come up with products to treat autoimmune diseases such as lupus and arthritis. They have secured the rights to this project by patenting the antibodies.[25]


  Conclusion Top


We can conclude by saying that ILs help in motility, cell growth, and differentiation. Various types of IL have been discovered to have major associations with diseases such as arthritis, psoriasis, cancer, and many more. Particularly, some ILs contributes more significantly than others in various diseases due to their mechanisms. Future applications are being up taken by various companies to come up with drugs to combat diseases related to ILs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor b, and TNF-a: Receptors, functions, and roles in diseases. J Allergy Clin Immunol 2016;138:984-1010.  Back to cited text no. 17
    
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Nold-Petry CA, Rudloff I, Baumer Y, Ruvo M, Marasco D, Botti P, et al. IL-32 promotes angiogenesis. J Immunol 2014;192:589-602.  Back to cited text no. 19
    
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23.
Vinluan F. Eli Lilly Pays Nektar $150M Up Front for Autoimmune Drug Rights. Available from: https://xconomy.com/ indiana/2017/07/24/eli-lilly-pays-nektar-150m-up-front-forautoimmune-drug-rights/. [Last accessed on 2020 Jul 19].  Back to cited text no. 23
    
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Abstract
Introduction
Mechanism
Significance
Future Perspectives
Conclusion
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