Generality
Immunosuppressants - as can easily be deduced from their name - are drugs capable of suppressing the patient's immune system .
Currently, several immunosuppressants are available in clinical practice. Of course, the type of active ingredient, the dose to be used and the duration of treatment will depend on the pathology that must be treated and the condition of each patient. In any case, generally, an attempt is made to adopt a therapeutic strategy that provides for the administration of associations of immunosuppressants, 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.
Below, the main classes of immunosuppressive drugs used in therapy will be briefly described.
Glucocorticoids
Glucocorticoids are drugs with anti-inflammatory and immunosuppressive activity. In this regard, the immunosuppressive drugs of first choice in the treatment of many autoimmune diseases are considered.
These active ingredients, in fact, have proved particularly effective both in the initial induction of immunosuppression, and in its maintenance.
Prednisone, prednisolone and dexamethasone belong to this class of drugs.
Action mechanism
Glucocorticoids exert their immunosuppressive activity - as well as anti-inflammatory activity - by interacting with their own receptor present at the cytoplasmic level. Subsequently, the complex formed by this interaction migrates into the nucleus, where it binds to DNA in specific sites, thus influencing gene transcription which, in turn, induces or not protein synthesis.
Thanks to this particular mechanism of action, glucocorticoids are able to block the synthesis of pro-inflammatory prostaglandins and leukotrienes, thus performing their task as immunosuppressive drugs.
Side effects
The main side effects that can occur following the use of glucocorticoids are: increased sweating, hoarseness, increased appetite, capillary fragility, fatigue, agitation and aggression.
Furthermore, 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 consists in the prevention of rejection in transplants, although they are also used in the treatment of various autoimmune diseases.
Action mechanism
Ciclosporin 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, ciclosporin 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, you may experience renal failure, hypertension, hyperlipidemia and diabetes.
antiproliferative
Sirolimus and methotrexate belong to the category of immunosuppressants with antiproliferative activity.
These active ingredients act with different mechanisms of action from one another. 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 renal transplantation. Generally, it is given in combination with ciclosporin or corticosteroids.
This drug exerts its action of suppressing the immune system by inhibiting a particular protein, called "target of rapamycin in mammals" (or mTOR, from "mammalian target of rapamycin"). This protein, in fact, is implicated in the multiplication of activated T cells. As a result, its inhibition promotes the onset of immunosuppression.
Sirolimus has a lower nephrotoxicity than calcineurin inhibitors. However, this active ingredient is able to enhance the toxic action that cyclosporine exerts against the kidneys. Therefore, it is very important that during the course of immunosuppressive therapy with these drugs, renal function is carefully and constantly monitored.
Furthermore, sirolimus can cause side effects such as hyperlipidemia, 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 ingredient also has interesting immunosuppressive properties, which make it possible to use (at low doses) in the treatment of different types of autoimmune diseases.
The main side effects that can occur after taking 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 - that can recognize and bind in a highly specific way to other particular types of proteins, called antigens.
In therapy, different types of monoclonal antibodies are available which are used for the treatment of various diseases, such as, for example, tumors and autoimmune diseases.
In the following, some of the main monoclonal antibodies currently used in the treatment of autoimmune diseases, such as, for example, rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis will be briefly described.
Rituximab
Rituximab is an anti-lymphocyte B monoclonal antibody. Once taken, this active ingredient binds to its antigen, located on the cell membrane of B lymphocytes, promoting its 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 high blood pressure or hypotension, skin rash, fever and throat irritation may occur.
infliximab
Infliximab is an anti-TNF-α monoclonal antibody. Human TNF-α (or tumor necrosis factor-alpha) is one of the mediators of inflammation implicated in the aforementioned autoimmune diseases.
Therefore - although it cannot be considered as a real immunosuppressant drug - by blocking the action of this chemical mediator, infliximab still manages to alleviate the symptoms induced by these pathologies.
The main side effects that can occur with the use of this drug are: nausea, diarrhea, abdominal pain, headache, dizziness, erythema, hives and tiredness.
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 in detail, these drugs - lowering the body's defenses in a rather marked manner - make the patient more susceptible to the contraction of infections, in particular the contraction of opportunistic infections.
Naturally, in the event of the appearance of any type of infection, it is necessary to immediately provide for their treatment, 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.
