CYTOKINES THERAPY : A NATURAL ALTERNATIVE TO ANTIBIOTICS FOR ORGANIC POULTRY PRODUCTION
Poultry are usually reared under intensive conditions which are conducive to infection by opportunistic pathogens. Newly hatched chickens are highly susceptible to infection during the first 2 weeks of life. Several factors contribute to this problem, including immaturity of their immune system, declining maternal antibodies level, and stress factor associated with intensive rearing of poultry. A major problem faced by all livestock industries, is loss of productivity due to disease, which is of major concern. Therefore, considerable measures are required in order to maintain the health status of these animals. The two main mechanisms by which the disease is controlled, involves the use of vaccines and antibiotics. Antibiotics have been used to treat and control diseases in livestock and poultry for more than 50 years. In-feed antibiotics are generally used at low levels and result in improvements in growth rate and feed-conversion efficiency. Antibiotics generally provide short-term, broad-spectrum protection and are provided continuously to poultry as feed additives. The use of antibiotics has become very popular in the poultry industries because, in addition to being an antimicrobial, they also have growth promoting activity. However, the extensive use of antibiotics as feed additives has raised concerns about the potential spread of antibiotic-resistant bacteria, in the food chain and unwanted residues in food products. As recently reported from a WHO meeting held in Berlin on the medical impact of the use of antimicrobials in food animals, the extensive use of antibiotics, particularly those that are used in human medicine, has resulted in human health concerns. The WHO has recently urged meat producers to stop using the same antibiotics that are used in humans. Furthermore, the WHO has emphasize the search for environmentally-friendly alternatives methods to control disease in livestock animals. A novel approach in the search for alternative therapeutics has been to examine cytokines as potential replacements for in-feed antibiotics in poultry.
Cytokines are proteins that are naturally produced by the body’s immune system immediately following infection or vaccination, resulting in protection from disease. They determine both the type and extent of an immune response that is generated following infection with a pathogen. These proteins exert either suppressive or enhancive effects on cellular proliferation, differentiation, activation, and motility. Cytokines control and promote immune responses in all animal species and therefore represent excellent candidates as therapeutics. In order to grow an animal, it has to be free from illness and stress. Growth is influenced by interactions between the immune system and other systems within the body such as the neurological and endocrine systems in which, cytokines play a crucial role. One of the most characterized chicken cytokine genes is chicken (Ch) IFN-ã. Treatment with ChIFN-ã results in enhanced growth rates in healthy chickens as well as in chickens infected with E. acervulina. The utilization of cytokines as an alternative to antibiotics in livestock animals, particular poultry, has become more feasible with the recent cloning of cytokine genes and the progression of new technologies such as live vectors. Since the chicken’s immune system is similar to that of mammals, they offer an attractive model system with which to study the effectiveness of cytokine therapy in the control of disease in intensive livestock. Under such conditions, the use of cytokines as nonspecific potentiators of the immune system may be a more practical solution to protection from infectious diseases. Cytokines potentially provides the animal production industries with the most natural, nonantibiotic methods for increasing disease resistance in chickens and offer an exciting alternative to antibiotics. Therefore, the use of cytokines as an effective, naturally occurring growth promoter is now an emerging area of research and use of cytokines in poultry will become an essential component of disease management in the future.
Cytokine therapy has been taken as a natural alternative for disease control. Disease control in food production animals is normally mediated through the use of vaccines, chemicals and antibiotics. However, the extensive use of antibiotics and chemicals in livestock has resulted in environmental and human health concerns, particularly with regard to the emergence of drug-resistant bacteria in the food chain. In fact, the World Health Organisation (WHO) has now urged meat producers to use environmentally-friendly alternative methods to control disease. Cytokines, as natural mediators of the immune response, offer exciting alternatives to conventional therapeutics. The utilisation of cytokines is becoming more feasible with the recent cloning of a number of cytokine genes. Since the chicken’s immune system is similar to that of mammals, they offer an attractive model system with which to study the effectiveness of cytokine therapy in the control of disease in intensive livestock.
Cytokine therapy has proven to be a novel therapeutic approach in treating patients with advanced malignancies. The purpose of this type of therapy is to manipulate the immune response in such a way as to generate the appropriate immune effector cells to eradicate solid tumors. Cytokine therapy is administrated only after the conventional form of therapies have been performed such as chemotherapy, radiotherapy, and surgery. Various regimens of cytokine administration have been implemented in eradicating solid tumors in patients with melanoma and renal cell cancer. There have been clinical trials executed involving the administration of interferon-gamma, interferon-alpha, Interleukin-2, tumor necrosis factor-alpha, and Interleukin-12. Advances in cytokine therapy have been thwarted by the relatively high level of toxicity associated with the administration of cytokines. Common toxicities include nausea, vomiting, fever/chills, fatigue, and headache. Dose escalation of a particular cytokine halts once three patients at a particular dose level experience grade three toxicity. The maximum tolerated dose of the cytokine is designated as the preceding dose. In turn, determining the schedule of treatment is another challenge at hand for clinicians. Partial or complete tumor regression has been noted in some clinical trials which offers hope in finding the appropriate cytokine or combination of cytokines and dose level to effectively treat advanced malignancies without being too toxic to the patient.
Advances in the understanding of the role of cytokines in immune and inflammatory disorders have led to the development of cytokine-based therapies. Therapies have been developed with the express aim to block/inhibit or restore the activity of specific cytokines. Cytokines delivered by gene therapy and antisense oligonucleotide treatment are also being assessed. Currently, the most utilized approach to cytokine therapy is that of blocking or neutralizing cytokine action with monoclonal antibodies (mAbs). Drugs that block inflammatory cytokines, such as tumor necrosis factor (TNF)- α, are among the most successful therapeutics approved for clinical use.
Cytokine immunotherapy
Immunotherapy is a medical term defined as the “treatment of disease by inducing, enhancing, or suppressing an immune response”. The active agents of immunotherapy are collectively called immunomodulators. They are a diverse array of recombinant, synthetic and natural preparations, often cytokines, such as granulocyte colony-stimulating factor (G-CSF), interferons, imiquimod and cellular membrane fractions from bacteria are already licensed for use in patients. Others including IL-2, IL-7, IL-12, various chemokines, synthetic cytosine phosphate-guanosine (CpG), oligodeoxynucleotides and glucans are currently being investigated extensively in clinical and preclinical studies.
Cytokines Meaning – The name “cytokine” comes from a combination of two Greek words: “cyto” which means cell and “kinos” which means movement. Cytokines are cell signalling molecules that let cells communicate with one another during immune responses and promote cell migration to sites of inflammation, infection, and trauma.
Chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors are examples of cytokines, although hormones and growth factors are not (despite some overlap in the terminology). Endothelial cells, fibroblasts, and other stromal cells all produce cytokines, as do immune cells including macrophages, B lymphocytes, T lymphocytes, and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells. They act through cell surface receptors and are particularly essential in the immune system; cytokines control the maturation, development, and responsiveness of specific cell types, as well as the balance between humoral and cell-based immune responses. In intricate ways, certain cytokines boost or inhibit the function of other cytokines. Hormones, which are also crucial cell signalling chemicals, are not the same. Hormones are produced by certain types of cells and circulate in larger concentrations. Cytokines play a role in host immunological responses to infection, inflammation, trauma, sepsis, cancer, and reproduction in both health and illness.
Types of Cytokines
The Different Types of Cytokines are Given Below:
- Interferons
- Chemokines
- Interleukins (many interleukins are considered to be lymphokines)
- TNF (tumour necrosis factor)
Interferons
Proteins called interferons prevent viruses from reproducing. Interferons are released when a cell is attacked by a virus. This instructs other cells to raise their defences in order to prevent the virus from spreading. As a result, interferons prevent a virus from spreading. Natural killer T-cells are also activated by interferons. These cells aid in the virus’s struggle by eliminating infected cells.
Chemokines
Chemokines are a type of cytokine that attracts cells to an infection location. Chemotaxis is the ability of a cell to summon other cells by sending a chemical communication. This fact explains why this sort of cytokine is called chemokine: it causes chemotaxis. Chemokines are the battle’s coordinators. When a foreign substance is discovered, for example, chemical commands are given to immune cells, which include diverse white blood cells. These cells then proceed to the threat’s location in order to eradicate it.
Interleukins
Proteins called interleukins govern immunological and inflammatory responses. They are mostly produced by white blood cells. Their role is to deliver messages to other white blood cells, informing them that it is time for them to report for duty. Interleukins is a simple name to remember because inter means between cells and leukins means leukocytes. Interleukins allow leukocytes to communicate with one another. Interleukins come in a variety of forms, each with a specific function in the immune system. Immune cells’ development, maturation, and activation are among these functions.
Tumour Necrosis Factor
TNF (tumour necrosis factor) is a type of cytokine that has the ability to kill cells, including cancer cells. TNF is produced by a variety of cells, although macrophages produce the most. It has the ability to connect to cancer cells and destroy them once released.
Cytokine Receptors
Cytokine receptors are glycoproteins on the cell surface that bind to cytokines and transmit their signals. These receptors allow cells to communicate with the extracellular environment by responding to signals generated nearby or elsewhere in the organism. Thus, the first binding of cytokines to their receptors is a critical process that occurs quickly, at extremely low cytokine concentrations, is almost always irreversible, and results in intracellular alterations that lead to a physiological response. The physiological response varies depending on the cytokine receptor and the cell, but it often involves gene expression, cell cycle alterations, and the release of mediators such as cytokines.
After going through the cytokines meaning it is very clear that it deals with the cell movement and signalling. The cloning of cytokine receptors revealed strong structural and functional conservation, justifying their classification as a superfamily of cytokine receptors. However, it is becoming obvious that structurally comparable subfamilies exist within this superfamily, with some receptors or receptor subunits being more linked to one another than to other members of the receptor superfamily. The TPO receptor (TPOR), for example, is more closely related to the EPO receptor (EPOR) and c than to other cytokine receptors.
Cytokine Therapy
For illness control, cytokine treatment has been used as a natural alternative. Vaccines, pesticides, and antibiotics are typically used to control disease in food production animals. The widespread use of antibiotics and pesticides in livestock, on the other hand, has raised environmental and human health issues, particularly with regard to the rise of drug-resistant bacteria in the food chain. In fact, the World Health Organization (WHO) has recently recommended meat producers to control the disease using environmentally acceptable alternatives. Cytokines, as natural mediators of the immune response, provide promising new treatment options. With the recent cloning of a number of cytokine genes, the use of cytokines is becoming more viable. Because the immune system of chickens is comparable to that of mammals, they make an appealing model system for studying the efficacy of cytokine treatment in disease control in intensive livestock.
In the treatment of patients with advanced cancers, cytokine therapy has proven to be a unique therapeutic technique. The goal of this sort of therapy is to modulate the immune response in order to develop the right immune effector cells in order to eliminate solid tumours. Cytokine therapy is used only after traditional therapies such as chemotherapy, radiation, and surgery have been exhausted. Various cytokine injection regimens have been used to eradicate solid tumours in melanoma and renal cell carcinoma patients. Clinical trials including the delivery of interferon-gamma, interferon-alpha, interleukin-2, tumour necrosis factor-alpha, and interleukin-12 have been conducted.
The relatively high level of toxicity associated with the administration of cytokines has stymied advances in cytokine therapy. Nausea, vomiting, fever/chills, lethargy, and headache are all common side effects. When three patients at a given dose level experience grade three toxicity, dose escalation for that cytokine comes to a halt. The preceding dose is marked as the cytokine’s maximum tolerable dose. Determining the therapy schedule, on the other hand, is a challenge for clinicians. Some clinical trials have shown partial or complete tumour regression, providing optimism for discovering the right cytokine or combination of cytokines and dose level to effectively treat advanced malignancies without being too harmful to the patient.
The development of cytokine-based therapeutics has resulted from advances in our understanding of the role of cytokines in immunological and inflammatory illnesses. Specific cytokine therapies have been created with the goal of blocking, inhibiting, or restoring their activity. Gene therapy-delivered cytokines and antisense oligonucleotide treatment are also being investigated. Blocking or neutralising cytokine effect with monoclonal antibodies is now the most widely used strategy to cytokine treatment (mAbs). Inflammatory cytokine inhibitors, such as tumour necrosis factor (TNF)-, are among the most effective treatments authorised for clinical usage.
What are Cytokines Sources?
Many cell groups produce cytokines, although helper T cells (Th) and macrophages are the most common. During physiological and pathological processes, resident and recruited macrophages, mast cells, endothelial cells, and Schwann cells may generate cytokines in and by peripheral nerve tissue.
- What is the Function of Cytokines?
Answer. Cytokines are tiny soluble proteins that give instructions to immune and non-immune cells and mediate communication between them. A set of cytokines important for macrophages’ role as innate immune system sentinels who mediate the transition from innate to adaptive immunity.
- Are Cytokines Good or Bad?
Answer. Cytokines have a wide range of roles in the immune system’s response to disease, and medications that modify their action have resulted in some remarkable treatments. When activating the immune system to fight a foreign infection or kill tumours, cytokines may be “beneficial.”
- What Cytokines Do in Inflammation?
Answer. Cytokines are proteins that control how the body reacts to infection, inflammation, and trauma. Some cytokines aggravate disease (proinflammatory cytokines), while others help to reduce inflammation and promote healing (anti-inflammatory cytokines) (anti-inflammatory cytokines).
Compiled & Shared by- Team, LITD (Livestock Institute of Training & Development)
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Reference-On Request.
