Cytokine Therapy

Cytokine therapy

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.