Related Terms

• Allergic, allergic reaction, allergic response, antibody, antifungal, antiviral, antiviral activity, autoimmune, autoimmunity, hypersensitive, hypersensitivity, immune, immune defense system, immune deficiency, immune disease, immune disorder, immune enhancement, immune function, immune reaction, immune response, immune stimulant, immune stimulation, immune suppression, immune system, immunoglobulin, immunoglobulin deficiency, immunomodulation, immunomodulator, immunostimulant, immunostimulation, immunosuppression, infection, inherited immune disorder, leukopenia, low white blood cell count, mononucleosis, primary immune deficiency, secondary immune deficiency, vaccine adjunct, viral infection, weakened immune system.

Background

• Immune system disorders occur when the body's immune system does not function properly. The immune system is a complex network of cells, proteins, tissues, and organs that work together to fight off harmful substances and disease-causing microorganisms called pathogens. A healthy immune system helps protect the body from disease, infection, and cancer.

• An immune system disorder can be classified as either an autoimmune disorder or an immune deficiency.

• Autoimmune disorders occur when the immune system mistakes body cells for harmful invaders, such as bacteria, and attacks them. Autoimmune disorders can destroy body tissues, cause abnormal organ growth, and/or impair organ function.

• Immune deficiencies occur when an individual's ability to fight against an infectious disease is compromised or entirely absent. Patients who suffer from immune deficiencies experience recurrent infections, such as sinusitis and pneumonia. There are two main types of immune deficiencies: primary immune deficiencies and secondary immune deficiencies.

• Primary immune deficiencies are disorders that occur because part of the body's immune system does not function properly. These disorders are caused by intrinsic or genetic defects in the immune system. Some primary immune deficiencies are inherited, which means they are passed down through family members. Individuals who have primary immune deficiencies are born with the disorders.

• The World Health Organization (WHO) has identified nearly 100 primary immune deficiency diseases, including X-linked agammaglobulinemia (Bruton's Disease), common variable immune deficiency (CVID), and selective immunoglobulin A deficiency.

• Many individuals affected by primary immune deficiency diseases require life-long therapies, such as intravenous immune globulin infusions, antibiotic therapies, or bone marrow transplantations.

• Secondary immune deficiencies are caused by factors outside of the body, such as chemotherapy treatment, radiation therapy, malnutrition, HIV infection, and diabetes. In addition, diseases, such as leukemia and multiple myeloma, cause cancerous immune cells to infiltrate the bone marrow, which is responsible for producing immune system cells. Secondary immune deficiency also occurs among critically ill patients and the elderly.

• Secondary immune deficiencies usually resolve once the underlying illness is treated or the outside factor is eliminated. For instance, immune deficiencies caused by chemotherapy or radiation therapy generally resolve once the treatment is completed.

Causes

• Autoimmunity: Researchers have not yet discovered what triggers the immune system to attack itself.

• Primary immune deficiencies: Primary immune deficiencies are caused by intrinsic or genetic defects in the immune system. Many primary immune disorders are passed down through families (inherited). This happens when a child inherits mutated genes or chromosomes associated with a particular disorder.

• For instance, some patients may be born with low levels of immunoglobulin antibodies. Antibodies are an important part of the immune system because they identify harmful substances that enter the body and trigger other immune cells to destroy the invading substance. Examples of antibody deficiencies include common variable immunodeficiency (CVID), transient hypogammaglobulinemia of infancy, and X-linked hypogammaglobulinemia.

• Secondary immune deficiencies: Secondary immune deficiencies are caused by factors outside of the body, such as chemotherapy treatment, radiation therapy, malnutrition, HIV infection, and diabetes. These outside factors weaken the immune system, making the patient vulnerable to disease and infection. In addition, cancers, such as leukemia and multiple myeloma, cause cancerous immune cells to infiltrate and damage the bone marrow, which is responsible for producing immune system cells. Secondary immune deficiency also occurs among critically ill patients or the elderly.

Signs and Symptoms

• Autoimmunity: Symptoms of autoimmune disease vary widely depending on the specific disease. There are more than 80 autoimmune disorders, all of which have unique symptoms. Autoimmune disorders typically lead to the destruction of an organ or tissue, which results in decreased function of the affected organ or tissue. For instance, if cells in the pancreas are destroyed, then it may lead to diabetes. Many autoimmune disorders also cause the organ or tissue to enlarge. For instance, Grave's disease causes thyroid enlargement (goiter formation). A group of nonspecific symptoms, including fatigue, dizziness, general feeling of discomfort, and fever, often accompanies autoimmune diseases.

• Primary and secondary immune deficiencies: Patients with immune deficiencies typically suffer from frequent infections, such as pneumonia. Patients are also more likely to develop certain cancers.

Complications

• Infections and cancer: Patients with weakened immune deficiencies have increased risks of developing infections and cancer. This is because the immune system is the body's first line of defense against disease-causing microorganisms and cancerous cells. In severe cases, infections or cancer may lead to death.

Diagnosis

• Fluorescent antinuclear antibody test (FANA): The fluorescent antinuclear antibody (FANA) test is usually performed if an autoimmune disorder is suspected. The FANA test is a blood test used to detect abnormal antibodies called autoantibodies. The autoantibodies bind to components of an individual's cells and cause the immune system to attack the body.

• During the procedure, a sample of blood is taken from the patient and sent to a laboratory. If autoantibodies are present in the blood, then the patient has an autoimmune disorder.

• In rare occasions, the FANA test results may be positive in people who do not have autoimmune disease. This is called a false-positive test result. The frequency of false-positive test results increases with age. A false negative result is also possible, but it is uncommon.

• Cytogenetic analysis: A cytogenetic analysis is a test used to detect chromosomal instability, which is a characteristic of some primary immune deficiencies, including Nijmegen breakage syndrome (NBS). During the procedure, a sample of the patient's blood is taken and the patient's chromosomes are stained during specific stages of replication. The sample is then observed to determine if chromosomal abnormalities are present.

• DNA analysis: A DNA analysis is used to detect genetic mutations associated with a particular disorder. During the procedure, a sample of blood is taken from the patient and analyzed at a laboratory for genetic mutations associated with particular immune deficiencies.

• Prenatal testing: A pregnant mother may have her fetus tested for genetic disorders. In order to retrieve a sample of the fetus' cells for testing, amniocentesis or chorionic villus sampling may be performed. During amniocentesis, a long, thin needle is inserted into the pregnant woman's abdominal wall and into the uterus. A small amount of fluid is removed from the sac surrounding the fetus. During chorionic villus sampling (CVS), a small piece of tissue, called chorionic villi, is removed from the placenta. There are risks associated with both of these procedures, including miscarriage. Patients should discuss the potential risks and benefits of these procedures with their healthcare providers.

• Nephelometry: A nephelometry blood test may be performed to diagnose certain antibody deficiencies. The test quickly and accurately measures the amount of immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA) in the patient's blood. Patients with antibody deficiencies will have reduced levels of one or more of these antibodies in their blood. A special lab chemical, called anti-immunoglobulin, is added to the patient's blood sample. A medical instrument then measures the movement of particles that is caused by the interaction between immunoglobulins and anti-immunoglobulins in a substance. Healthy individuals have 45-250 milligrams of IgM per deciliter of blood, 560-1,800 milligrams of IgG per deciliter of blood, and 100-400 milligrams of IgA per deciliter of blood,

• Enzyme-linked immunosorbent assay (ELISA): An enzyme-linked immunosorbent assay (ELISA) measures the level of IgG subclasses in the blood. There are four types of IgG: IgG1, IgG2, IgG3, and IgG4. In healthy individuals, 60-70% of IgG antibodies in the bloodstream are IgG1, 20-30% are IgG2, 5-8% are IgG3, and 1-3% are IgG4. Individuals who have lower levels of one or more subclasses of IgG are diagnosed with IgG subclass deficiency.

Treatment

• Immunosuppressants: Autoimmunity is controlled through balanced suppression of the immune system. The goal of treatment is to minimize the immune response against body cells without completely eliminating the immune response toward harmful invaders. Corticosteroids and immunosuppressant medications, including cyclosporine(Gengraf®, Neoral®, or Sandimmune®) and azathioprine (Azasan® or Imuran®) are commonly used to reduce the immune response. Immunomodulatory therapies, such as etanercept (Enbrel®), have been shown to be useful in treating some autoimmune disorders, including rheumatoid arthritis. Side effects of immunosuppressants may lead to severe infections because these drugs weaken the immune system.

• Anti-inflammatories: Anti-inflammatories are often used to treat autoimmune disorders. Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin® or Advil®) or celecoxib (Celebrex®), have been used to relieve pain and reduce inflammation in patients suffering from autoimmune disorders, such as rheumatoid arthritis.

• Antimicrobials: Medications called antimicrobials are used to treat infections in patients with immune deficiencies. Antimicrobials kill the disease-causing organism. Antibiotics are used to treat bacterial infections; antivirals are used to treat viral infections; and anti-fungals are used to treat fungal infections. These medications may be taken by mouth, applied to the skin or eyes, or injected into a vein. The specific dose and duration of treatment depends on the type and severity of the infection and the patient's overall health.

• Bone marrow transplant (BMT): A bone marrow transplant (BMT) can be performed in patients who have life-threatening immune deficiencies, such as severe combined immunodeficiency (SCID) and Wiskott-Aldrich syndrome. A successful BMT can permanently cure primary immune deficiencies.

• However, not everyone is a candidate for a bone marrow transplant. The transplant must come from a donor whose body tissues are a close biological match to the recipient. Serious health risks are also associated with the procedure, as with any major surgery. Individuals who have weakened immune systems are at risk of developing graft-versus-host disease after surgery. This condition occurs when the transplanted bone marrow attacks the recipient's weakened immune system. Other recipients may experience transplant rejection, which occurs when the body's immune system attacks the donated organ.

• Interferon-gamma injections: Interferon-gamma injections have been used to treat certain immune deficiencies. Interferon-gamma solutions contain cytokines, which are natural chemicals produced by immune cells during an immune response. For instance, interferon-gamma injections are commonly used to treat a condition called chronic granulomatous disease. This disease is caused by faulty white blood cells, called phagocytes, which ingest and destroy foreign substances that enter the body. Interferon injections have been shown to activate the phagocytes and help restore the immune response in these patients.

• Intravenous immune globulin (IVIG): Intravenous immune globulin (IVIG) consists of immunoglobulin antibodies extracted from 3,000-10,000 healthy blood donors. In some instances, blood from as many as 100,000 donors is used. The U.S. Food and Drug Administration (FDA) has approved IVIG for the treatment of primary immune deficiencies.

• Immune globulin products contain sterile, purified immunoglobulin G (IgG). The products typically contain more than 95% unmodified IgG and only trace amounts of immunoglobulin A (IgA) or immunoglobulin M (IgM). IgG antibodies are the smallest, but most abundant antibodies in the body and make up 75-80% of all the antibodies in the body. They are present in all body fluids. The IgG antibodies are considered the most important antibodies for fighting against bacterial and viral infections, and they are the only antibodies that can cross the placenta during pregnancy. IgA antibodies are primarily found in the nose, airway passages, digestive tract, ears, eyes, saliva, tears and vagina. These antibodies protect body surfaces that are frequently exposed to foreign organisms and substances from outside of the body. IgM antibodies are present in the blood and lymph fluids, and they are the first antibodies that are produced in response to an infection.

• The immune globulin is typically injected for about two to four hours a day for two to seven days. The patient usually receives another single dose every 10-21 days, or every three to four weeks depending on the condition. Patients typically start responding to treatment after eight days.

• Side effects from IVIG occur in less than five percent of patients, according to researchers. Common side effects typically occur immediately after infusions and may include flushing (reddening of the cheeks), headache, chills, dizziness, increased sweating, leg cramps, pain and tenderness at the injection site, tiredness, muscle pain, lower back pain, nausea, and low blood pressure. Immunoglobulin levels should be tested to make sure the patient does not have an IgA deficiency. Individuals who are IgA deficient should not receive IVIG because they may experience a severe allergic reaction called anaphylaxis.

• IVIG is available in different concentration (strengths). The U.S. Food and Drug Administration (FDA) has approved Gammagard S/D®, Gammar-P IV®, Gamimune-N®, Iveegam®, Polygam® S/D, Sandoglobulin® Venoglobulin-I®, Venoglobulin-S®, Carimune/Panglobulin®, Gamunex®, and Baxter AG®.

Integrative Therapies

• Good scientific evidence:

• Ginseng: For more than 2,000 years, the roots of ginseng have been valued in Chinese medicine. Several studies suggest that ginseng may be an effective agent for immune system enhancement. Additional high quality research is needed before a conclusion be made.

• Avoid with known allergy to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in ginseng formulations.

• Probiotics: Probiotics are beneficial bacteria that are sometimes called friendly germs. They help maintain a healthy intestine and help the body digest foods. They also help keep harmful bacteria and yeasts in the gut under control. Most probiotics come from food sources, especially cultured milk products. Research suggests that probiotics, especially those in milk or food, may be an effective agent for immune system enhancement. However, commercially produced yogurt may not be as effective. More studies are needed, particularly with yogurt, to give recommendations.

• Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

• Zinc: Zinc formulations have been used since ancient Egyptian times to enhance wound healing. Zinc appears to be an essential trace element for the immune system, but research on the effect of zinc supplementation on immune function is scant and mostly focuses on patients with specific diseases. Zinc gluconate appears to exert beneficial effects on immune cells, improving CD3 and CD4 counts and increasing CD4/CD8 ratios in children. There are relatively few studies that examine zinc levels and the effects of zinc supplementation on the health of the elderly population. Further research is needed before a recommendation can be made.

• Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.

• Unclear or conflicting scientific evidence:

• Acupuncture: It is unclear if acupuncture can help increase white blood cells in patients with chemotherapy-induced leukopenia. Well-designed research is needed to better determine the potential effectiveness of acupuncture for this indication.

• Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, infections, bleeding disorders, medical conditions of unknown origin, or neurological disorders. Avoid if taking drugs that increase the risk of bleeding (e.g. anticoagulants). Avoid on areas that have received radiation therapy and during pregnancy. Use cautiously with pulmonary disease (e.g. asthma or emphysema). Use cautiously in elderly or medically compromised patients, diabetics, or with history of seizures. Avoid electroacupuncture with arrhythmia (irregular heartbeat) or in patients with pacemakers because therapy may interfere with the device.

• Amaranth oil: Amaranth is grown in Asia and the Americas and harvested primarily for its grain, which is used as a food source for bread, pasta, and infant food. Limited evidence suggests that amaranth may stimulate the immune system when combined with a heart-healthy diet in patients with heart disease and high cholesterol. However, additional studies of amaranth alone are needed to determine if it is effective for immunomodulation.

• Amaranth is generally considered safe. Avoid if allergic or sensitive to amaranth. Use cautiously with diabetes, low blood sugar, low blood pressure, immune system disorders, or kidney disorders. Use cautiously if pregnant or breastfeeding.

• Arabinogalactan: Arabinogalactans belong to a group of carbohydrates called polysaccharides. When consumed in the diet, arabinogalactan comes from the wood of the larch tree (Larix species) and is approved for use as a dietary fiber by the U.S. Food and Drug Administration (FDA). Early research has suggested that arabinogalactan may cause immune stimulation; however, its effect on immunity in healthy volunteers is not clear. More evidence is needed.

• Avoid if allergic or sensitive to arabinogalactan or larch. People who are exposed to arabinogalactan or larch dust may have irritation of the eyes, lungs, or skin. Use cautiously in people with diabetes, digestive problems, or immune system disorders, and in people who consume diets high in fiber or low in galactose. Arabinogalactan should not be used during pregnancy or breastfeeding.

• Arginine (L-arginine): L-arginine helps maintain the body's fluid balance (urea, creatinine), and aids in wound healing, hair growth, sperm production (spermatogenesis), blood vessel relaxation (vasodilation), and fights infection. Preliminary study results suggest that arginine may cause immunomodulation. More studies are needed to confirm these results.

• Avoid if allergic to arginine or with a history of stroke or liver or kidney disease. Avoid if pregnant or breastfeeding. Use cautiously if taking blood-thinning drugs (like warfarin or Coumadin®) or blood pressure drugs or herbs or supplements with similar effects. Blood potassium levels should be monitored. L-arginine may worsen symptoms of sickle cell disease. Caution is advised in patients taking prescription drugs to control sugar levels.

• Astragalus: In traditional Chinese medicine (TCM), astragalus is commonly found in mixtures with other herbs. Western herbalists began using astragalus in the 1800s as an ingredient in various tonics. Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. Reliable human studies are lacking. High quality human research is necessary before a firm conclusion can be drawn.

• Avoid if allergic to astragalus, peas, or any related plants or with a history of Quillaja bark-induced asthma. Avoid with aspirin or aspirin products or herbs or supplements with similar effects. Avoid with inflammation or fever, stroke, transplant, or autoimmune diseases. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with a risk of bleeding. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, or diuretics or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.

• Beta-carotene: Beta-carotene is a member of the carotenoids, which are very colorful (red, orange, yellow), fat-soluble compounds. They are naturally found in many fruits, grains, oil, and vegetables, including green plants, carrots, sweet potatoes, squash, spinach, apricots, and green peppers. Preliminary research of beta-carotene for immune system enhancement shows mixed results. Further research is needed before a conclusion can be drawn.

• Avoid if sensitive to beta-carotene, vitamin A or any other ingredients in beta-carotene products.

• Black currant: The black currant shrub is native to Europe and parts of Asia and is particularly popular in Eastern Europe and Russia. There is currently a lack of information in humans on the effectiveness of black currant seed for immunomodulation.

• Avoid if allergic or hypersensitive to black currant, its constituents, or plants in the Saxifragaceae family. Avoid with hemophilia or in those taking blood thinners, unless otherwise recommended by a qualified healthcare provider. Use cautiously with venous disorders or gastrointestinal disorders. Use cautiously if taking MAOIs (antidepressants) or vitamin C supplements. Avoid if pregnant or breastfeeding.

• Bovine colostrum: Bovine colostrum is the pre-milk fluid produced from cow mammary glands during the first two to four days after birth. Bovine colostrum confers growth, nutrient, and immune factors to the offspring. Bovine colostrum contains immunoglobulins or antibodies that are released into the bloodstream in response to infections. These immunoglobulins may help improve immune function and may be effective in treating immune system deficiencies. More evidence is required before a firm conclusion can be made.

• Avoid if allergic or hypersensitive to dairy products. Use bovine colostrum with caution. Toxic compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlordiphenyldichloroethylene (DDE) have been found in human colostrum and breast milk. Thus, it is possible that these agents may be found in bovine colostrum. Avoid with, or if at risk of developing, cancer. Use cautiously with immune system disorders, atherosclerosis (hardening of the arteries) or if taking medications, such as anti-diarrheal agents (e.g. immodium), insulin, or CNS agents (amphetamines, caffeine). Avoid if pregnant or breastfeeding.

• Cat's claw: Cat's claw is widely used in the United States and Europe, and it is one of the top herbal remedies sold despite a lack of high-quality human evidence. Preliminary research of cat's claw for immune system enhancement shows mixed results. Further research is needed before a conclusion can be drawn.

• Avoid if allergic to Cat's claw or Uncaria plants or plants in the Rubiaceae family such as gardenia, coffee, or quinine. Avoid with a history of conditions affecting the immune system (such as AIDS, HIV, some types of cancer, multiple sclerosis, tuberculosis, rheumatoid arthritis, or lupus). Use cautiously with bleeding disorders or history of stroke, or if taking drugs that may increase the risk of bleeding. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with bleeding risks. Cat's claw may be contaminated with other Uncaria species. Reports exist of a potentially toxic, Texan grown plant, Acacia gregii being substituted for cat's claw. Avoid if pregnant, breastfeeding, or trying to become pregnant.

• Copper: Copper is a mineral that occurs naturally in many foods, including vegetables, legumes, nuts, grains, fruits, shellfish, avocado, beef, and animal organs, (e.g. liver and kidney). Copper is involved in the development of immune cells and immune function in the body. Severe copper deficiency appears to have adverse effects on immune function, although the exact mechanism is not clear.

• Avoid if allergic/hypersensitive to copper. Avoid use of copper supplements during the early phase of recovery from diarrhea. Avoid with hypercupremia, occasionally observed in disease states, including cutaneous leishmaniasis, sickle-cell disease, unipolar depression, breast cancer, epilepsy, measles, Down syndrome, and controlled fibrocalculous pancreatic diabetes (a unique form of secondary diabetes mellitus). Avoid with genetic disorders affecting copper metabolism such as Wilson's disease, Indian childhood cirrhosis, or idiopathic copper toxicosis. Avoid with HIV/AIDS. Use cautiously with water containing copper concentrations greater than 6mg/L. Use cautiously with anemia, arthralgias, or myalgias. Use cautiously if taking oral contraceptives. Use cautiously if at risk for selenium deficiency. The U.S. Recommended Dietary Allowance (RDA) is 1,000 micrograms for pregnant women. The U.S. RDA is 1,300 micrograms for nursing women.

• Echinacea: Echinacea is a perennial herb that has been used to treat a variety of medical conditions. Echinacea has been studied alone and in combination preparations for immune system stimulation. It remains unclear if there are clinically significant benefits. Additional studies are needed in this area before conclusions can be drawn regarding safety or effectiveness.

• Avoid if allergic to echinacea, its constituents, or any members of the Asteraceae/Compositae family (ragweed, chrysanthemums, marigolds, daisies). Use cautiously in patients prone to atopic reactions and in those with hemochromatosis and diabetes. Some natural medicine experts discourage the use of echinacea by people with conditions affecting the immune system, such as HIV/AIDS, some types of cancer, multiple sclerosis, tuberculosis, and rheumatologic diseases (such as rheumatoid arthritis or lupus). Use parenteral preparations of echinacea(no longer approved for use in Germany) cautiously. Use tinctures cautiously with alcoholic patients or in patients taking disulfiram or metronidazole. Avoid using echinacea in patients presenting for anesthesia. Use cautiously if pregnant or breastfeeding.

• Gamma linolenic acid (GLA):Gamma linolenic acid (GLA) is a dietary fatty acid that is found in many plant oil extracts. Few clinical trials have investigated the effect of GLA on immune responses in healthy human subjects. GLA, as blackcurrant seed oil, may offer some benefits. Further study is required to determine if GLA is beneficial for immune enhancement.

• Use cautiously with drugs that increase the risk of bleeding like anticoagulants and anti-platelet drugs. Avoid if pregnant or breastfeeding.

• Goldenseal: Goldenseal is one of the five top-selling herbal products in the United States. Goldenseal is sometimes suggested to be an immune system stimulant. However, there is little clinical evidence in this area. More research is needed before a firm conclusion can be drawn.

• Avoid if allergic or hypersensitive to goldenseal or any of its constituents (like berberine and hydrastine). Use cautiously with bleeding disorders, diabetes, or low blood sugar levels. Avoid if pregnant or breastfeeding.

• Maitake mushroom: Maitake mushrooms (Grifola frondosa) are fungi that can be eaten. Maitake has been used both as a food and for medical conditions. Beta-glucan extracts from maitake have been studied for immune stimulation. Additional high quality research is needed to make a conclusion.

• Maitake has not been studied thoroughly in humans, and its effects are not well known. Because it has been used historically as a food, it is thought that low doses may be safe. Avoid if allergic or hypersensitive to maitake or its constituents. Use cautiously with low blood pressure, diabetes, or low blood sugar. Use cautiously if taking blood pressure medications, antidiabetic agents, immunostimulants, immunosuppressants, or interferons. Avoid if pregnant or breastfeeding.

• Massage: The main goal of massage is to help the body heal itself. Touch is fundamental to massage therapy and is used by therapists to locate painful or tense areas, to determine how much pressure to apply, and to establish a therapeutic relationship with clients. Preliminary evidence suggests that massage therapy may preserve immune function. Further research is needed before a firm conclusion can be made.

• Avoid with bleeding disorders, low platelet counts, or if taking blood-thinning medications (such as heparin or warfarin/Coumadin®). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery, or blood clots. Use cautiously with a history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.

• Meditation: Many forms of meditation have been practiced for thousands of years throughout the world, with many techniques originating in Eastern religious practices. Preliminary research reports increased antibody response after meditation. Further study is needed to better determine if meditation affects immune function.

• Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professionals before starting meditation and should explore how meditation may or may not fit in with their current treatment plans. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses.

• Mistletoe: Once considered a sacred herb in Celtic tradition, mistletoe has been used for centuries for high blood pressure, epilepsy, exhaustion, anxiety, arthritis, vertigo (dizziness), and degenerative inflammation of the joints. A few small trials found mistletoe to be promising as an immunostimulant in individuals with the common cold. Further study is needed to determine if mistletoe is effective for immunomodulation.

• Avoid if allergic or hypersensitive to mistletoe or to any of its constituents. Anaphylactic reactions (life threatening shock) have been described after injections of mistletoe. Avoid with acute, highly febrile, inflammatory disease, thyroid disorders, seizure disorders, or heart disease. Use cautiously with diabetes, glaucoma, or if taking cholinergics.

• Probiotics: Lactobacillus fermentum (CECT5716) may increase the protective effects of the flu vaccine. More research is needed regarding the use of probiotics as a vaccine adjunct.

• Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

• Qi gong: Qi gong is a type of traditional Chinese medicine (TCM) that is thought to be at least 4,000 years old. It is traditionally used for spiritual enlightenment, medical care, and self-defense. There is some evidence suggesting that internal Qi gong may help with treatment of immune deficiencies. However, the evidence is still unclear, and further research is needed to understand how Qi gong may potentially benefit immune function. Based on preliminary study, Chan-Chuang Qi gong therapy may be used to treat leukopenia (low white blood cell count) in breast cancer patients treated with chemotherapy. Further study is warranted.

• Qi gong is generally considered to be safe in most people when learned from a qualified instructor. Use cautiously with psychiatric disorders.

• Reflexology: Reflexology involves the application of manual pressure to specific points or areas of the feet called "reflex points" that are believed to correspond to other parts of the body. Some research suggests that self-administered reflexology may be beneficial for immune enhancement. Additional study is needed in this area.

• Avoid with recent or healing foot fractures, unhealed wounds, or active gout flares affecting the foot. Use cautiously and seek prior medical consultation with osteoarthritis affecting the foot or ankle or with severe vascular disease of the legs or feet. Use cautiously with diabetes, heart disease, unstable blood pressure, cancer, active infections, past episodes of fainting (syncope), mental illness, gallstones, kidney stones, or with a pacemaker. Use cautiously if pregnant or breastfeeding. Reflexology should not delay diagnosis or treatment with more proven techniques or therapies.

• Rose hip: Rose hips are the fruits that develop from the blossoms of the wild rose plant. It is unclear if rose hips affect immune function. More studies are needed in this area.

• Avoid if allergic to rose hips, rose pollen, their constituents, or members of the Rosaceae family. Use cautiously if taking anticoagulant or anti-platelet aggregating agents, anticancer agents, anti-HIV medications, anti-inflammatory agents, antilipemics, aluminum-containing antacids, antibiotics, salicylates or salicylate-containing herbs, or laxatives. Use cautiously in patients who are avoiding immune system stimulants.

• Shiitake: Lentinan, a constituent of shiitake, has been shown to modulate the immune system in some studies. However, there is currently a lack of reliable human evidence supporting the use of lentinan or shiitake for immunomodulation. Additional study is needed in this area.

• Avoid if allergic or hypersensitive to shiitake mushrooms. Avoid if pregnant or breastfeeding.

• Tai chi: Tai chi is a system of movements and positions believed to have developed in 12th Century China. Tai chi techniques aim to address the body and mind as an interconnected system and are traditionally believed to have mental and physical health benefits to improve posture, balance, flexibility, and strength. Tai chi may increase the body's immune response in older adults. For example, patients receiving varicella vaccines and who practiced tai chi showed increased immune responses. Although early study is promising, more study is needed to better determine if tai chi is effective for immune system stimulation.

• Avoid with severe osteoporosis or joint problems, acute back pain, sprains, or fractures. Avoid during active infections, right after a meal, or when very tired. Some believe that visualization of energy flow below the waist during menstruation may increase menstrual bleeding. Straining downwards or holding low postures should be avoided during pregnancy, and by people with inguinal hernias. Some tai chi practitioners believe that practicing for too long or using too much intention may direct the flow of chi (qi) inappropriately, possibly resulting in physical or emotional illness. Tai chi should not be used as a substitute for more proven therapies for potentially serious conditions. Advancing too quickly while studying tai chi may increase the risk of injury.

• Taurine: Currently, there is insufficient available evidence to recommend for or against the use of taurine as a vaccine adjunct.

• Taurine is an amino acid and it is unlikely that there are allergies related to this constituent. However, allergies may occur from multi-ingredient products that contain taurine. Use cautiously in patients with high cholesterol, low blood pressure, coagulation disorders, potential for mania, or epilepsy. Avoid consumption of energy drinks containing taurine, caffeine, glucuronolactone, B vitamins, and other ingredients, then consuming alcohol or exercising. Use cautiously if pregnant or breastfeeding.

• Thymus extract: Thymus extracts for nutritional supplements are usually derived from young calves (bovine). Preliminary evidence suggests that thymus extract increases white blood cell counts. Additional study is needed to determine if thymus extract is effective for immune system stimulation.

• Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously due to the potential for exposure to the virus that causes "mad cow disease." Avoid use with an organ transplant or other forms of allografts or xenografts. Avoid with thymic tumors, myasthenia gravis (neuromuscular disorder), or untreated hypothyroidism. Avoid if taking hormonal therapy or immunosuppressants. Avoid if pregnant or breastfeeding; thymic extract increases human sperm motility and progression.

• Vitamin A: Vitamin A is a fat-soluble vitamin. Vitamin A deficiency may compromise immunity, but there is no clear evidence that additional vitamin A supplementation is beneficial for immune function in patients who are not vitamin A deficient.

• Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity may occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses; however, vitamin A excess, as well as deficiency, has been associated with birth defects. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.

• Vitamin B6: Major sources of vitamin B6 include: cereal grains, legumes (beans), vegetables (like carrots, spinach, peas), potatoes, milk, cheese, eggs, fish, liver, meat, and flour. Vitamin B6 has been shown to be important for immune system function in older individuals. One study found that the amount of vitamin B6 required to reverse immune system impairments in elderly people was more than the current recommended dietary allowance (RDA). Well-designed clinical trials on vitamin B6 supplementation for this indication are needed before a conclusion can be made.

• Vitamin B6 is likely safe when used orally in doses not exceeding the recommended dietary allowance (RDA). Avoid if sensitive or allergic to any vitamin B6 product ingredients. Some individuals seem to be particularly sensitive to vitamin B6 and may have problems at lower doses. Avoid excessive dosing. Use cautiously if pregnant or breastfeeding.

• Vitamin D: Vitamin D is found in many foods, including fish, eggs, fortified milk, and cod liver oil. The sun also helps the body produce vitamin D. Preliminary human evidence suggests that vitamin D and its analogues, such as alfacalcidol, may act as immunomodulatory agents. High quality clinical studies are needed to better understand the effects of vitamin D on immunomodulation.

• Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended doses; doses higher than recommended may cause toxic effects. Use cautiously with hyperparathyroidism (overactive thyroid), kidney disease, sarcoidosis, tuberculosis, and histoplasmosis. Vitamin D is safe in pregnant and breastfeeding women when taken in recommended doses.

• Vitamin E: Vitamin E exists in eight different forms ("isomers"): alpha, beta, gamma and delta tocopherol; and alpha, beta, gamma, and delta tocotrienol. Alpha-tocopherol is the most active form in humans. Studies of the effects of vitamin E supplementation on immune system function have yielded mixed results. Further research is needed before a clear conclusion can be drawn.

• Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid doses greater than the recommended daily level in pregnant women and breastfeeding women.

• Fair negative scientific evidence:

• DHEA: DHEA (dehydroepiandrosterone) is a hormone that is produced by the adrenal glands. It is suggested by some textbooks and review articles that DHEA may be effective for immune system stimulation. However, current scientific evidence does not support this claim.

• Avoid if allergic to DHEA. Avoid with a history of seizures. Use cautiously with adrenal or thyroid disorders or if taking anticoagulants or drugs, herbs, or supplements for diabetes, heart disease, seizure, or stroke. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with bleeding risks. Avoid if pregnant or breastfeeding.

• Lycopene: Lycopene is a carotenoid found in human serum, and skin, liver, adrenal, lung, prostate, and colon tissue. It has been proposed that lycopene and other carotenoids, such as beta-carotene, may stimulate the immune system. However, several studies of lycopene supplements and tomato juice intake in humans do not report effectiveness for immune stimulation.

• Avoid if allergic to tomatoes or to lycopene. Due to a lack of conclusive data, avoid if pregnant or breastfeeding.

Prevention

• Intravenous immune globulin (IVIG) may help prevent infections in patients who have weakened immune systems.

• Patients should talk to their healthcare providers about recommended vaccinations. Patients who are born with immune deficiencies should not receive live virus vaccines, such as the oral polio, measles, or chicken pox. This is because live viral vaccines can sometimes infect the recipient if he/she is immunocompromised. In some cases, immunocompromised individuals can become infected after coming into close contact with a recently vaccinated individual.

• Some secondary immune deficiencies can be prevented by avoiding or minimizing exposure to disease-causing organisms (pathogens), such as bacteria or viruses. Individuals should regularly wash their hands with soap and water and avoid close contact with individuals who have contagious infections or diseases.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. American Academy of Allergy Asthma & Immunology (AAAAI). www.aaaai.org.

2. Asthma and Allergy Foundation of America (AAFA). www.aafa.org.

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4. National Institute of Allergy and Infectious Diseases. www3.niaid.nih.gov.

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