Immunosuppressant

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Immunosuppressants are substances that reduce the functions of the immune system . Immunosuppressive drugs are z. B. used in the following indications:

These drugs are not without side effects and risks. In particular with the less selective acting substances there is a limitation of the defense mechanisms due to the main effect, which increases the risk of infection and facilitates the multiplication and spread of malignant cells in the organism - i.e. the risk of cancer.

Active ingredient groups

Glucocorticoids

Glucocorticoids , such as prednisolone or dexamethasone , are part of most immunosuppressive therapy regimens. They act in the very early phases of the immune reaction and mediate their effects through various mechanisms. They intervene in the transcription of cytokines and thus suppress their synthesis. Thereby they inhibit the activation of lymphocytes , reduce the development of the monocytes into macrophages and inhibit the phagocytic activity of the macrophages.

Cytostatics

Most cytostatics have an immunosuppressive effect. Used as immunosuppressants mainly

used.

antibody

Polyclonal and monoclonal antibodies are available for immunosuppression . The polyclonal antibodies include polyclonal antithymocyte globulins , which are used for the prophylaxis of rejection reactions. Due to the pioneering work of Milstein, Köhler and Jerne, a large number of monoclonal antibodies have been developed and introduced into therapy in the last few decades. A tabular list can be found under monoclonal antibodies .

Calcineurin inhibitors

  • Ciclosporin is a cyclic polypeptide consisting of 11 amino acids that is obtained from the fungus Tolypocladium inflatum . It inhibits both the humoral and the cellular immune response. The ciclosporin-ciclophilin complex formed in the T-cell inhibits the activity of the protein phosphatase calcineurin and consequently the IL-2 synthesis and thus the T-cell proliferation.
  • Tacrolimus is macrolide lactone produced by Streptomyces tsukubaensis . Like cyclosporine, it acts as an inhibitor of calcineurin , but is more potent and has a more favorable side-effect profile.
  • Pimecrolimus is also a macrolide lactone that is structurally related to tacrolimus.

TOR inhibitors

  • Sirolimus (rapamycin) and everolimus are macrolides. The Actinobacterium Streptomyces hygroscopicus produces Sirolimus, Everolimus is a derivative of Sirolimus. Sirolimus and everolimus inhibit the mTOR complex ( mammalian target of rapamycin ), a central control molecule for cell reproduction. Both mTOR inhibitors thus inhibit the proliferation of B and T cells.

Others

  • Belatacept, a soluble fusion protein consisting of the extracellular domain of the human cytotoxic T lymphocyte antigen 4 (CTLA-4) and the Fc domain of the human IgG1 antibody.
  • Fingolimod , a synthetic replica of the natural active ingredient Myriocin from the mushroom Isaria sinclairii used in traditional Chinese medicine . The substance binds indirectly to the sphingosine-1-phosphate receptor (S1P receptor) and thereby causes T and B cells to withdraw from the blood system into the lymph nodes.
  • Fumaric acid dimethyl ester has an immunomodulating effect in a previously unknown way and is approved for psoriasis and multiple sclerosis .
  • With long-term use, opioids can weaken both innate and acquired immunity. It is believed that this is due to an interaction with the opioid receptors on immune cells . However, this effect is an undesirable one.

See also

further reading

Individual evidence

  1. ↑ a b Mutschler drug effects: textbook of pharmacology, clinical pharmacology and toxicology; with introductory chapters in anatomy, physiology and toxicology. Stuttgart, WVG, 2013. 10th, completely revised and expanded edition.
  2. ↑ Susanne Donner: Cancer risk increases massively after organ donation In: derbund.ch, September 11, 2018, accessed on September 11, 2018.