Immunosuppression

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Dr. med. Philipp Nicol is a freelance writer for the medical editorial team.

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In the case of immunosuppression, the body's own defense system (immune system) is suppressed - either through an illness or increased stress or specifically with medication. For example, drugs for immunosuppression are used after an organ transplant and in various autoimmune diseases. Read more about the topic here: When is immunosuppression indicated as a therapy? What are the risks? What do I have to take to care of?

What is immunosuppression?

If the body's own immune system is suppressed so that it can no longer work properly, it is called immunosuppression. Depending on the extent, the body's defenses are only weakened or even completely disabled. If you want to understand why immunosuppression can be both undesirable and wanted, you first have to understand how the immune system works.

Basics of the immune system

The immune system of our body has the task of eliminating pathogens (e.g. viruses, bacteria), pollutants from the environment and also pathogenic cell changes (cancer cells). This happens via different mechanisms and with the participation of different organs (e.g. spleen, lymph nodes), cell types (especially white blood cells = leukocytes) and proteins (such as antibodies).

With regard to the defense mechanisms, a distinction is made between non-specific defense (innate immune system) and specific defense (acquired immune system). The unspecific immune defense is present from birth and can generally (unspecific) ward off pathogens. This happens, for example, with the help of skin and mucous membranes (form a barrier against invading pathogens), "phagocytes" (type of white blood cells that "eat up" foreign substances), natural killer cells (type of white blood cells that can kill infected and cancer cells) as well as various proteins (such as cytokines as messenger substances of the immune system).

A very targeted fight against pathogens is possible with the specific immune defense. These include the so-called B lymphocytes - special white blood cells that can produce specific antibodies against a pathogen when they first come into contact with a pathogen - matching characteristic proteins (antigens) on the intruder's surface.

The body's own cells also carry various proteins on their surface. Normally these are correctly recognized as "own" by the immune system and left alone. Sometimes, however, the immune system is misdirected - the immune system attacks the body's own proteins and destroys them. Then one speaks of an autoimmune disease.

Immunosuppression as a therapy, side effect or symptom

For the treatment of autoimmune diseases, one deliberately induces an immunosuppression in the patient in order to limit the misdirected behavior of the immune defense. Even after a transplant, patients are given immunosuppressive drugs. This is to prevent the immune system from attacking and rejecting the foreign organ.

Chemotherapy and radiation therapy (radiation) are often used to treat cancer. Both therapies cause immunosuppression in the patient as a side effect.

In addition, immunosuppression can be a symptom of various diseases. Two well-known examples are blood cancer (leukemia) and AIDS.While in leukemia the body itself produces defective white blood cells (leukocytes) and thus weakens the immune system, in the case of AIDS a pathogen - the HI virus - destroys certain leukocytes. The immune system is sometimes weakened even after major psychological or physical stress.

When do you perform immunosuppression?

There are two main areas of application for artificially induced immunosuppression - i.e. immunosuppressive therapy -: autoimmune diseases and organ transplants. The immune system is specifically weakened because it would otherwise harm the patient. However, the degree of intervention is different in the two cases.

Immunosuppression after an organ transplant

An organ transplant involves the implantation of another person's organ in a patient. The new organ is recognized as foreign by the immune system and is therefore attacked - organ rejection occurs.

In this case, the immune system is only doing its job, but if it is not suppressed, the consequences for the patient are life-threatening. Unfortunately, after an organ transplant, there is no other option than lifelong immunosuppression. That means: The patient has to take medication permanently, which dampen the immune reactions.

Immunosuppression in autoimmune diseases

With an autoimmune disease, the immune system is disturbed and directed against the own body (auto: Greek for self). Artificial immunosuppression is supposed to suppress this misdirection of the immune system. Examples of autoimmune diseases treated with immunosuppressive therapy:

• Rheumatoid arthritis
• Connective tissue diseases (collagenoses: dermatomyositis / polymyositis, systemic lupus erythematosus)
• Inflammation of the blood vessels (vasculitis)
• Chronic inflammatory bowel disease (Crohn's disease, ulcerative colitis)
• autoimmune liver inflammation (autoimmune hepatitis)
• Pulmonary fibrosis, sarcoid
• Multiple sclerosis (MS)
• Myasthenia gravis
• Inflammation of the kidney corpuscles (glomerulonephritis) - a type of kidney inflammation

What do you do with immunosuppression?

Therapeutic immunosuppression can be divided into two parts:

• Induction phase: At the beginning, the doctor gives a high dose of medication in order to achieve high concentrations of the active ingredient in the blood as quickly as possible (induction). Usually three or four different immunosuppressive drugs are combined (triple or quadruple therapy).
• Maintenance phase: after a certain period of time (e.g. three to 12 months after organ transplantation) this high dose of immunosuppressants can then be reduced and continued as maintenance therapy with two to three drugs.

Most autoimmune diseases come on in flare-ups. Particularly strong intervention is required during such a flare-up of inflammation (induction therapy). In the remission phases, in which the disease is "dormant", the immune system is usually dampened with a significantly lighter active ingredient (maintenance therapy). The aim is to prevent or at least postpone a new inflammatory flare-up as far as possible.

Immunosuppressive drugs (immunosuppressants)

Immunosuppressants are drugs that can suppress immune reactions selectively (such as monoclonal antibodies) or non-specific (such as glucocorticoids, calcineurin inhibitors). The most important are:

Calcineurin inhibitors

Calcineurin is an enzyme that is found in various cells in the body, including certain cells of the immune system. There it is important for signal transmission. Calcineurin inhibitors prevent this signal transmission and thus the activation of the immune system. Calcineurin inhibitors that are particularly frequently used for immunosuppression are ciclosporin and tacrolimus.

Cell division inhibitors

Cell division inhibitors (cell proliferation inhibitors) prevent rapidly dividing cells from multiplying. These cells include cancer cells on the one hand, but also immune cells on the other. Cell division inhibitors are therefore suitable for the treatment of cancer and autoimmune diseases.

Depending on the point of attack, a distinction is made between cytostatics (such as azathioprine, mycophenolic acid = MPA and mycophenolate mofetil = MMF) and mTOR inhibitors (such as everolimus and sirolimus).

antibody

Man-made antibodies are also used for immunosuppression (e.g. infliximab, adalimumab, rituximab). These are among the so-called biologicals - these are biotechnologically manufactured drugs.

The therapeutic antibodies bind specifically to proteins of various immune cells and thereby inhibit them. They are used for certain autoimmune diseases and tumor diseases, but not for immunosuppression after an organ transplant.

Since the biologicals inhibit the immune system particularly strongly, they must not be administered in certain situations (e.g. during pregnancy or in the event of an acute or chronic infection).

Glucocorticoids ("cortisone")

Glucocorticoids (glucocorticosteroids or steroids for short) are hormones that occur naturally in the body on the one hand (produced by the adrenal cortex) and on the other hand are synthetically produced and administered as drugs. These synthetic glucocorticoids have, among other things, strong anti-inflammatory and slightly immunosuppressive effects.

What are the risks of immunosuppression?

In a sense, therapeutic immunosuppression is a dilemma. On the one hand, you have to throttle the immune system, because otherwise it will cause damage (e.g. after an organ transplant). On the other hand, everyone needs functioning defenses in order to be able to defend themselves against pathogens, for example. In addition, the drugs used have a wide range of side effects.

Whether and to what extent these side effects occur depends very much on the disease in question and the amount of medication used.

Increased susceptibility to infections and tumors

A serious side effect of all immunosuppressants is the increased susceptibility to infection, especially at high dose levels. Even comparatively harmless infections such as colds can be life-threatening for a person with immunosuppression. The reason: The drugs not only suppress the unwanted effects of the immune system, but also the entire immune system. Pathogens can spread through the body much more easily. Therefore, even with small infections, those affected must immediately see a doctor and possibly a hospital, where they can be observed and treated quickly if necessary.

Patients with long-term immunosuppression are also at an increased risk of developing cancer. Because the weakened immune system no longer adequately recognizes and destroys degenerated cells, malignant neoplasms occur more often than in healthy people. Those affected should therefore be examined regularly for certain tumors (tumor screening).

Toxic effect on tissue (toxicity)

Most immunosuppressive drugs are nephrotoxic and neurotoxic, meaning that they have a toxic effect on the kidneys and nerve tissue. This can lead to impaired kidney function (renal insufficiency) or neurological symptoms (e.g. abnormal sensations).

Damage to the bone marrow (myelosuppression)

The bone marrow is also often attacked by immunosuppression. The formation of blood cells (red and white blood cells and platelets) is disturbed. Possible consequences are increased susceptibility to infection, anemia and increased tendency to bleed.

Increase in fat and sugar in the blood

Almost all immunosuppressants increase the blood lipid level (hyperlipidemia). Most of the time, this problem cannot be treated with a low-fat diet alone. This is why many patients are given additional fat-lowering drugs, such as statins.

Another side effect of many immunosuppressants (especially steroids) is increased blood sugar levels. Diabetes mellitus may even develop, which the doctor must regularly check and treat.

Osteoporosis and high blood pressure

Long-term treatment with steroids in particular can lead to a disruption of the bone metabolism - the result is osteoporosis with increased bone fractures. In addition, people who are immunosuppressed often develop high blood pressure. Both side effects must be treated with medication.

Gastrointestinal problems

Some immunosuppressants are poorly tolerated by the gastrointestinal tract. For example, mycophenolate mofetil or azathioprine can cause nausea, vomiting or diarrhea immediately after ingestion. These side effects can have a significant impact on an individual's quality of life. If you experience such problems from taking immunosuppressants, you should speak to your doctor.

What do I have to consider in the event of immunosuppression?

Therapeutic immunosuppression is a massive intervention with sometimes considerable side effects. However, it is often the only treatment option.

Immunosuppressants are administered in high doses immediately after a transplant. During this time, the immune system is very vulnerable, so contact with germs must be prevented as much as possible. Patients with a fresh transplant are therefore isolated and wear a face mask. Visitors must be healthy, even a small cold can be a danger to the transplant recipient.

Shaking hands, caressing and kissing are taboo at first - even if it's difficult. The same applies to cut flowers, fruit and fruit juices - they can be carriers of pathogens.

See a doctor immediately if any of the following warning signs occur shortly after an organ transplant:

• Fever or other signs of an infection (weakness, fatigue, cough, burning sensation when urinating)
• Pain in the area of ​​the transplanted organ
• decreased or increased urine output
• Weight gain
• Diarrhea or bloody stools

In both cases of therapeutic immunosuppression - after an organ transplant and with autoimmune diseases - the following applies: Make sure you take the prescribed immunosuppressants regularly. This is the only way to prevent organ rejection or alleviate an autoimmune disease. You should also have the concentration of the medication in the blood checked regularly.

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