Immunological agents are drugs that modify the immune response either by enhancing or suppressing the immune system.
Immune stimulant: drug used to energize the immune system when it is exhausted from fighting prolonged invasion or needs help fighting a specific pathogen or cancer cell
Immune suppressant: drug used to block or suppress the actions of the T cells and antibody production; used to prevent transplant rejection and to treat autoimmune diseases
There are two types of immunological agents which include;
IMMUNE STIMULANTS
Interferons
interferon alfa-2b
interferon alfacon-1
interferon alfa-n3
interferon beta-1a
interferon beta-1b
interferon gamma-1b
peginterferon alfa-2a
peginterferon alfa-2b
Interleukins
aldesleukin
oprelvekin
IMMUNE SUPPRESSANTS
T- and B-Cell Suppressors
abatacept
alefacept
azathioprine
Interleukin-Receptor Antagonist
anakinra
Monoclonal Antibodies
adalimumab
alemtuzumab
basiliximab
bevacizumab
certolizumab
Immunostimulants
Interferons
Interferons are substances naturally produced and released by human cells that have been invaded by viruses
They may also be released from cells in response to other stimuli, such
as cytotoxic T cell activity. A number of interferons are now available for
use.
Several are produced by recombinant DNA technology, which include Interferon alfa-n3 (Alferon N) is produced by harvesting human leukocytes. Interferon beta-1a (Avonex) is produced from Chinese hamster ovary cells. Interferon gamma-1b (Actimmune) is produced by Escherichia coli bacteria. The interferon of choice depends on the condition being treated
Therapeutic Action
The desired and beneficial actions of interferons are as follows:
- Preventing virus particles from replicating inside cells.
- Stimulating interferon receptor sites on non-invaded cells to produce antiviral proteins, which prevent viruses from entering the cell.
- They inhibit tumor growth and replication.
- They stimulate cytotoxic T-cell activity.
- Interferons enhance inflammatory response.
- Interferon gamma-1b also acts like an interleukin, stimulating phagocytes to be more aggressive.
Pharmacokinetics
The interferons are generally well absorbed after subcutaneous or intramuscular injection. They have a rapid onset of action and peak within 3 to 8 hours. They are broken down in the liver and kidneys and seem to be excreted primarily through the kidneys.
Indications
- Treatment of chronic hepatitis C in adults
- Treatment of multiple sclerosis in adults
- Treatment of leukemias, Kaposi sarcoma, warts, AIDS-related complex, and malignant melanoma.
Contraindications
- Allergy to any interferons or product component.
- Pregnancy. Many of the interferons are teratogenic in animals and therefore should not be used during pregnancy.
- Lactation. It is advised that the drugs not be used during lactation unless the benefits to the mother clearly outweigh any risks to the baby.
- Cardiac disease. Hypertension and arrhythmias have been reported with the use of these drugs.
- Myelosuppression: These drugs may suppress the bone marrow.
Adverse Effects
The adverse effects associated with the use of interferons are related to the immune or inflammatory reaction that is being stimulated (stimulating the immune and inflammatory response causes a
- Flu-like syndrome with lethargy, myalgia, arthralgia, anorexia, nausea)
- Headache
- Dizziness
- Bone marrow depression
- Depression
- Suicidal ideation
- Liver impairment
- Photosensitivity
Interleukins
Interleukins are a type of cytokine, ‘any of a group of naturally occurring proteins’ that mediate communication between cells (lymphocytes)
This communication stimulate cellular immunity by increasing the activity of
natural killer cells, platelets, and cytokines, and inhibit tumor growth.
Two interleukin preparations are available for use. Aldesleukin (Proleukin) is a human interleukin produced by recombinant DNA technology using E. coli bacteria. Oprelvekin (Neumega) is a newer agent that is also produced by DNA technology.
Indications
- Treatment of specific renal carcinomas in adults
- Prevention of severe thrombocytopenia
Contraindications
- Allergy to any interleukins or E-coli-produced product.
- Pregnancy: These drugs were shown to be embryocidal and teratogenic in animal studies.
- Lactation: Potential adverse effects to the baby as it is not clear whether drugs can cross into breast milk.
- Renal, liver, cardiovascular impairment
Immunosuppressants
Immune suppressants (as already listed above) often are used in conjunction with corticosteroids, which block the inflammatory reaction and decrease initial damage to cells.
They are especially beneficial in cases of organ transplantation and in the
treatment of autoimmune diseases. The immune suppressants include T- and B-cell suppressors, an interleukin-receptor antagonist, and monoclonal antibodies.
T- and B-Cell Suppressors
Cyclosporine is the most commonly used immune suppressant.
Indications
- Prevention and treatment of specific transplant rejection.
- Treatment of rheumatoid arthritis
- Treatment of psoriasis.
- Reduction of the number of relapses in multiple sclerosis in adults.
Contraindications
- Known allergy to drug and its components.
- Pregnancy
- Lactation
- Renal or hepatic impairment.
- Known neoplasms. Potentially could spread with immune system suppression.
Adverse Effects
- Patients receiving these drugs are at increased risk for infection and for the development of neoplasms due to their blocking effect on the immune system.
- Hepatotoxicity
- Renal toxicity
- Renal
dysfunction - Pulmonary edema.
- Headache
- Tremors
- Secondary infections such as acne
- GI upset
- diarrhea
- hypertension.
Interleukin-Receptor Antagonist
An interleukin-receptor antagonist works to block the activity of the interleukins that are released in an inflammatory or immune response.
The only available interleukin receptor antagonist is anakinra (Kineret).
Indications
- Prevention of rejection after a transplant.
- Reduction of signs and symptoms of adults suffering from rheumatoid arthritis and helping them slow down structural damage of bones.
Contraindications
- Known allergy to E.coli–produced products or to anakinra itself.
- It should be used with caution during pregnancy and lactation because the drug may cross the placenta and enter breast milk.
- It also is used cautiously in patients with renal impairment, immunosuppression, or any active infection because these could be
exacerbated by the effects of the drug. - There is an increased risk of infection whenever this drug is used, and the patient needs to be protected from exposure to infections and monitored closely after any invasive procedures.
- Immunizations cannot be given while the patient is on interleukin-receptor antagonists.
Adverse Effects
- Headache
- Sinusitis
- Nausea
- Diarrhea
- Upper respiratory infections
- Injection-site reactions .
Monoclonal Antibodies
Monoclonal antibodies attach to specific receptor sites to exhibit their immune suppressor actions.
Monoclonal antibodies include adalimumab (Humira), alemtuzumab (Campath), basiliximab (Simulect), bevacizumab (Avastin), cetuximab (Erbitux), certolizumab (Cimzia), daclizumab (Zenapax)
Indications
- Prevention of renal transplant rejection
- Treatment of B-cell chronic lymphocytic leukemia
- Reduction of the signs and symptoms of Crohn disease
- Treatment of paroxysmal nocturnal hemoglobinuria, to reduce haemolysis.
- Treatment of B-cell non-Hodgkin lymphoma in conjunction with rituximab.
- Treatment of asthma with a very strong allergic component and seasonal allergic rhinitis not occasionally controlled by common medicine.
- Prevention of serious RSV(Respiratory syncytial virus) infection in high-risk children.
- Treatment of metastatic breast cancer.
- Treatment of psoriasis
Contraindications
- Monoclonal antibodies are contraindicated in the presence of any known allergy to the drug or to murine products and in the presence of fluid overload.
- They should be used cautiously with fever (treat the fever before beginning therapy)
- They should not be used during pregnancy or lactation unless the benefit clearly outweighs the potential risk to the fetus or neonate.
Adverse Effects
- The most serious adverse effects associated with the use of
monoclonal antibodies are acute pulmonary edema (dyspnea, chest pain, wheezing), which is associated with severe fluid retention. - Fever
- Chills
- Malaise
- Myalgia
- Nausea
- Diarrhea
- Vomiting
- Increased susceptibility to infection
- Intravascular hemolysis with resultant fatigue, pain, dark urine, shortness of breath, and blood clots.
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