Generality
Immunosuppressants - as can be easily deduced from their name - are drugs capable of suppressing the patient's immune system.
Currently, there are several immunosuppressants available in clinical practice. Of course, the type of active ingredient, the dose to be used and the duration of the treatment will depend on the pathology to be treated and on the condition of each patient. In any case, in general, an attempt is made to adopt a therapeutic strategy that involves the administration of immunosuppressive combinations, in such a way as to be able to use the lowest possible concentrations and in such a way as to minimize, as far as possible, the side effects and prevent resistance phenomena.
The main classes of immunosuppressive drugs used in therapy will be briefly described below.
Glucocorticoids
Glucocorticoids are drugs with anti-inflammatory and immunosuppressive activity. In this regard, they are considered the first choice immunosuppressive drugs in the treatment of many autoimmune diseases.
These active principles, in fact, have proved to be particularly effective both in the initial induction of immunosuppression and in its maintenance.
Prednisone, prednisolone and dexamethasone belong to this class of drugs.
Mechanism of action
Glucocorticoids exert their immunosuppressive activity - as well as the anti-inflammatory one - by interacting with their own receptor present at the cytoplasmic level. Subsequently, the complex formed by this interaction migrates to the nucleus, where it binds to DNA at specific sites, thus influencing gene transcription which, in turn, induces or does not induce protein synthesis.
Thanks to this particular mechanism of action, glucocorticoids are able to block the synthesis of pro-inflammatory prostaglandins and leukotrienes, thus carrying out their role as immunosuppressive drugs.
Side effects
The main undesirable effects that may occur following the use of glucocorticoids are: increased sweating, hoarseness, increased appetite, capillary fragility, asthenia, agitation and aggression.
In addition, late adverse effects may also occur, such as: hypertension, hyperlipidemia, diabetes, Cushing's syndrome, peptic ulcer and osteopenia.
Calcineurin inhibitors
Ciclosporin and tacrolimus belong to this category of immunosuppressive drugs. The main therapeutic indication of these active ingredients is the prevention of rejection in transplants, although they are also used in the treatment of various autoimmune diseases.
Mechanism of action
Cyclosporine and tacrolimus perform their action as immunosuppressive drugs through the inhibition of calcineurin.
Calcineurin is a protein involved in many important biological processes, among which we find the activation of lymphocyte cells, in particular that of T lymphocytes.
Therefore, by inhibiting the activity of the aforementioned protein, cyclosporine and tacrolimus are able to induce immunosuppression.
Side effects
The main adverse effect associated with the "use of" calcineurin inhibitors is nephrotoxicity. Furthermore, following a prolonged use of these drugs, one can suffer from renal failure, hypertension, hyperlipidemia and diabetes.
Antiproliferatives
Sirolimus and methotrexate belong to the category of immunosuppressants with antiproliferative activity.
These active ingredients act with different action mechanisms from each other. These mechanisms will be briefly described below.
Sirolimus
Sirolimus (also known as rapamycin) is an active ingredient widely used in the prevention of rejection in the case of a kidney transplant. It is usually given in combination with cyclosporine or corticosteroids.
This drug exerts its immune suppression action by inhibiting a particular protein, called "mammalian target of rapamycin" (or mTOR). This protein is involved in the multiplication of lymphocytes. T activated. Consequently, its inhibition favors the onset of immunosuppression.
Sirolimus has lower nephrotoxicity than calcineurin inhibitors. However, this active ingredient is able to enhance the toxic action that cyclosporine exerts on the kidneys. Therefore, it is very important that during immunosuppressive therapy with these drugs, kidney function is carefully and constantly monitored.
Furthermore, sirolimus can cause undesirable effects such as hyperlipidaemia, anemia, leukopenia and thrombocytopenia.
Methotrexate
Methotrexate is an anticancer drug belonging to the class of antimetabolites; for this reason, it is normally used in the treatment of tumors.
However, this active principle also possesses interesting immunosuppressive properties, which make it possible to use it (in low doses) in the treatment of various types of autoimmune diseases.
The main side effects that can occur following the intake of methotrexate are: nausea and vomiting, diarrhea, anorexia, skin rash, urticaria, Stevens-Johnson syndrome, headache, asthenia, renal dysfunction and hepatotoxicity.
Monoclonal Antibodies
Monoclonal antibodies are particular types of proteins - obtained with recombinant DNA techniques - capable of recognizing and binding in a highly specific manner to other particular types of proteins, defined as antigens.
In therapy there are different types of monoclonal antibodies that are used for the treatment of various pathologies, such as, for example, tumors and autoimmune diseases.
Some of the main monoclonal antibodies currently in use in the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, will be briefly described below.
Rituximab
Rituximab is a monoclonal antibody against B lymphocytes. Once taken, this active ingredient binds to its antigen, located on the cell membrane of B lymphocytes, promoting their lysis, therefore, death and thus inducing immunosuppression.
This antibody is mainly used in the treatment of rheumatoid arthritis and in the treatment of some types of lymphomas.
After taking rituximab, side effects such as hypertension or hypotension, rash, fever and throat irritation may occur.
Infliximab
Infliximab is a monoclonal anti-TNF-α antibody. Human TNF-α (or tumor necrosis factor-alpha) is one of the inflammatory mediators involved in the aforementioned autoimmune diseases.
Therefore - although it cannot be considered as a real immunosuppressive drug - by blocking the action of this chemical mediator, infliximab is still able to alleviate the symptoms induced by these pathologies.
The main side effects that may occur with the use of this drug are: nausea, diarrhea, abdominal pain, headache, dizziness, erythema, hives and fatigue.
Side effects
As we have seen, each immunosuppressive drug can cause different side effects.
However, there are some side effects common to all immunosuppressive drugs.
More specifically, these drugs - by lowering the body's defenses in a rather marked manner - make the patient more susceptible to the contraction of infections, in particular to the contraction of opportunistic infections.
Naturally, in the event of the appearance of any type of infection, it is necessary to immediately treat them, instituting a suitable therapy and, possibly, suspending the administration of the immunosuppressants.
However, this type of decision rests solely with the doctor treating the patient.
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