View source for Immunosuppressive drug

{{Short description|Drug that inhibits activity of immune system}}
{{More medical citations needed|date=February 2022}}
{{Use dmy dates|date=January 2024}}
[[File:Prednisone.svg|thumb|[[Prednisone]]]]
[[File:Dexamethasone structure.svg|thumb|[[Dexamethasone]]]]
'''Immunosuppressive drugs''', also known as '''immunosuppressive agents''', '''immunosuppressants''' and '''antirejection medications''', are [[medication|drugs]] that inhibit or prevent the activity of the [[immune system]].

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==Classification==
Immunosuppressive drugs can be classified into five groups:{{citation needed|date=January 2023}}
* [[#Glucocorticoids|glucocorticoid]]s
* [[#Cytostatics|cytostatic]]s
* [[#Antibodies|antibodies]]
* [[#Drugs acting on immunophilins|drugs acting on immunophilin]]s
* [[#Other drugs|other drugs]]

===Glucocorticoids===
{{Main|Glucocorticoid}}
In pharmacologic (supraphysiologic) doses, glucocorticoids, such as [[prednisone]], [[dexamethasone]], and [[hydrocortisone]] are used to suppress various [[allergy|allergic]], [[inflammation|inflammatory]], and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the [[transplant rejection|acute transplant rejection]] and [[graft-versus-host disease]]. Nevertheless, they do not prevent an infection and also inhibit later [[tissue reparation|reparative processes]].

====Immunosuppressive mechanism====
Glucocorticoids suppress [[cell-mediated immunity]]. They act by inhibiting [[gene expression]] of cytokines including [[Interleukin 1]] (IL-1), [[Interleukin 2|IL-2]], [[Interleukin 3|IL-3]], [[Interleukin 4|IL-4]], [[Interleukin 5|IL-5]], [[Interleukin 6|IL-6]], [[Interleukin 8|IL-8]], and TNF-alpha by binding to corticosteroid [[response element]]s on DNA.<ref>{{Cite book | vauthors = Jennings DL | veditors = DiPiro JT, Yee GC, Posey LM, Haines ST, Nolin TD, Ellingrod VL |title=Pharmacotherapy: A Pathophysiologic Approach |date=2020 |publisher=McGraw Hill Medical |isbn=978-1-260-11681-6 |edition=11th |location=United States of America |oclc=1142934194}}</ref> This decrease in [[cytokine]] production reduces [[T cell]] proliferation. With decreased T cell proliferation there is decreased production of IL-2. This further decreases the proliferation of T cells.<ref>{{cite journal | vauthors = Coutinho AE, Chapman KE | title = The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights | journal = Molecular and Cellular Endocrinology | volume = 335 | issue = 1 | pages = 2–13 | date = March 2011 | pmid = 20398732 | pmc = 3047790 | doi = 10.1016/j.mce.2010.04.005 }}</ref><ref>{{Cite book | vauthors = Schimmer BP, Funder JW |title=Goodman & Gilman's the pharmacological basis of therapeutics |publisher=McGraw Hill Medical |year=2018 |isbn=978-1-259-58473-2 | veditors = Shanahan JF, Lebowitz H |edition=13th |location=New York |oclc= 993810322}}</ref>

Glucocorticoids also suppress the [[humoral immunity]], causing [[B cell]]s to express smaller amounts of IL-2 and [[IL-2 receptor]]s. This diminishes both B cell clone expansion and [[antibody]] synthesis.

====Anti-inflammatory effects====
Glucocorticoids influence all types of inflammatory events, no matter their cause. They induce the [[lipocortin-1]] (annexin-1) synthesis, which then binds to [[cell membrane]]s preventing the [[phospholipase A2]] from coming into contact with its [[substrate (biochemistry)|substrate]] [[arachidonic acid]]. This leads to diminished [[eicosanoid]] production. The [[cyclooxygenase]] (both COX-1 and COX-2) expression is also suppressed, potentiating the effect.

Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the [[leukocyte]] membrane receptors and inhibits various inflammatory events: [[epithelium|epithelial]] [[cell adhesion|adhesion]], [[emigration]], [[chemotaxis]], [[phagocytosis]], [[respiratory burst]], and the release of various inflammatory mediators (lysosomal enzymes, cytokines, [[tissue plasminogen activator]], [[chemokine]]s, etc.) from [[neutrophil]]s, [[macrophage]]s, and [[mastocyte]]s.

===Cytostatics===
{{Main|Chemotherapy}}
[[Cytostatic]]s inhibit [[cell division]]. In immunotherapy, they are used in smaller doses than in the treatment of malignant diseases. They affect the proliferation of both T cells and B cells. Due to their highest effectiveness, [[purine]] analogs are most frequently administered.

====Alkylating agents====

The [[alkylating antineoplastic agent|alkylating agent]]s used in immunotherapy are [[mustard gas|nitrogen mustards]] ([[cyclophosphamide]]), [[nitrosourea]]s, [[platinum]] compounds, and others. Cyclophosphamide (Baxter's Cytoxan) is probably the most potent immunosuppressive compound. In small doses, it is very efficient in the therapy of [[systemic lupus erythematosus]], autoimmune [[hemolytic anemia]]s, [[granulomatosis with polyangiitis]], and other immune diseases. High doses cause [[pancytopenia]] and hemorrhagic [[cystitis]].

====Antimetabolites====

[[Antimetabolite]]s interfere with the synthesis of nucleic acids. These include:
* [[folic acid]] analogues, such as [[methotrexate]]
* [[purine]] analogues, such as [[azathioprine]] and [[mercaptopurine]]
* [[pyrimidine]] analogues, such as [[fluorouracil]]
* [[protein biosynthesis|protein synthesis]] inhibitors.

=====Methotrexate=====

[[Methotrexate]] is a [[folic acid]] analogue. It binds [[dihydrofolate reductase]] and prevents synthesis of [[tetrahydrofolate]]. It is used in the treatment of autoimmune diseases (for example rheumatoid arthritis or Behcet's Disease) and in transplantations.

=====Azathioprine and mercaptopurine=====

[[Azathioprine]] (Prometheus' Imuran), is the main immunosuppressive cytotoxic substance. It is extensively used to control transplant rejection reactions. It is nonenzymatically cleaved to [[mercaptopurine]], that acts as a purine analogue and an inhibitor of DNA synthesis. Mercaptopurine itself can also be administered directly.

By preventing the clonal expansion of [[lymphocyte]]s in the induction phase of the immune response, it affects both the [[cell immunity|cell]] and the [[humoral immunity]]. It is also efficient in the treatment of autoimmune diseases.

=====Cytotoxic antibiotics=====
Among these, [[dactinomycin]] is the most important. It is used in [[kidney transplantation]]s. Other cytotoxic antibiotics are [[anthracycline]]s, [[mitomycin C]], [[bleomycin]], [[mithramycin]].

===Antibodies===
{{see also|Biologics for immunosuppression}}
[[Antibody|Antibodies]] are sometimes used as a quick and potent immunosuppressive therapy to prevent the acute rejection reactions as well as a targeted treatment of lymphoproliferative or autoimmune disorders (e.g., anti-[[CD20]] monoclonals).

====Polyclonal antibodies====
Heterologous [[polyclonal antibodies]] are obtained from the [[blood plasma|serum]] of animals (e.g., [[rabbit]], [[horse]]), and injected with the patient's [[thymocyte]]s or lymphocytes. The antilymphocyte ([[Anti-lymphocyte globulin|ALG]]) and antithymocyte [[antigen]]s ([[Anti-thymocyte globulin|ATG]]) are being used. They are part of the steroid-resistant acute rejection reaction and grave [[aplastic anemia]] treatment. However, they are added primarily to other immunosuppressives to diminish their dosage and toxicity. They also allow transition to cyclosporin therapy.

Polyclonal antibodies inhibit T lymphocytes and cause their [[lysis]], which is both [[Complement system|complement]]-mediated cytolysis and cell-mediated [[opsonization]] followed by removal of [[reticuloendothelial]] cells from the [[circulatory system|circulation]] in the [[spleen]] and [[liver]]. In this way, polyclonal antibodies inhibit cell-mediated immune reactions, including graft rejection, [[delayed hypersensitivity]] (i.e., [[tuberculin]] skin reaction), and the [[graft-versus-host disease]] (GVHD), but influence [[thymus]]-dependent antibody production.

As of March 2005, there are two preparations available to the market: [[Atgam]], obtained from horse serum, and [[Thymoglobuline]], obtained from rabbit serum. Polyclonal antibodies affect all lymphocytes and cause general immunosuppression, possibly leading to [[post-transplant lymphoproliferative disorder]]s (PTLD) or serious infections, especially by [[cytomegalovirus]]. To reduce these risks, treatment is provided in a hospital, where adequate isolation from infection is available. They are usually administered for five days intravenously in the appropriate quantity. Patients stay in the hospital as long as three weeks to give the immune system time to recover to a point where there is no longer a risk of [[serum sickness]].

Because of a high [[immunogenicity]] of polyclonal antibodies, almost all patients have an acute reaction to the treatment. It is characterized by [[fever]], [[rigor]] episodes, and even [[anaphylaxis]]. Later during the treatment, some patients develop serum sickness or [[immune complex glomerulonephritis]]. Serum sickness arises seven to fourteen days after the therapy has begun. The patient has fever, [[joint pain]], and [[erythema]] that can be soothed with the use of steroids and [[analgesic]]s. [[Urticaria]] (hives) can also be present. It is possible to diminish their toxicity by using highly purified [[serum fraction]]s and intravenous administration in the combination with other immunosuppressants, for example, [[#Drugs acting on immunophilins|calcineurin inhibitors]], cytostatics, and [[corticosteroid]]s. The most frequent combination is to use antibodies and ciclosporin simultaneously in order to prevent patients from gradually developing a strong immune response to these drugs, reducing or eliminating their effectiveness.

====Monoclonal antibodies====
[[Monoclonal antibodies]] are directed towards exactly defined antigens. Therefore, they cause fewer side-effects. Especially significant are the [[IL-2 receptor]]- (CD25-) and CD3-directed antibodies. They are used to prevent the rejection of transplanted organs, but also to track changes in the lymphocyte subpopulations. It is reasonable to expect similar new drugs in the future.

=====T-cell receptor directed antibodies=====
[[Muromonab-CD3]] is a murine anti-CD3 monoclonal antibody of the IgG2a type that was previously used to prevent [[T-cell]] activation and proliferation by binding the T-cell receptor complex present on all differentiated T cells. As such it was one of the first potent immunosuppressive substances and was administered to control the steroid- and/or polyclonal antibodies-resistant acute rejection episodes. As it acts more specifically than polyclonal antibodies it was also used prophylactically in transplantations. However, muromonab-CD3 is no longer produced,<ref>{{cite journal | vauthors = Reichert JM | title = Marketed therapeutic antibodies compendium | journal = mAbs | volume = 4 | issue = 3 | pages = 413–415 | date = May 2012 | pmid = 22531442 | pmc = 3355480 | doi = 10.4161/mabs.19931 }}</ref> and this mouse monoclonal antibody has been replaced in the clinic with chimeric, humanized, or human monoclonal antibodies.

The muromonab's mechanism of action is only partially understood. It is known that the molecule binds TCR/CD3 receptor complex. In the first few administrations this binding non-specifically activates T-cells, leading to a serious syndrome 30 to 60 minutes later. It is characterized by fever, [[myalgia]], headache, and [[arthralgia]]. Sometimes it develops in a life-threatening reaction of the cardiovascular system and the central nervous system, requiring a lengthy therapy. Past this period CD3 blocks the TCR-antigen binding and causes [[conformational change]] or the removal of the entire TCR3/CD3 complex from the T-cell surface. This lowers the number of available T-cells, perhaps by sensitizing them for the uptake by the [[epithelial reticular cell]]s. The cross-binding of CD3 molecules as well activates an intracellular signal causing the T cell anergy or apoptosis, unless the cells receive another signal through a [[co-stimulation|co-stimulatory molecule]]. CD3 antibodies shift the balance from [[Th1 cell|Th1]] to [[Th2 cell]]s as CD3 stimulates Th1 activation.<ref>{{cite journal | vauthors = Smeets RL, Fleuren WW, He X, Vink PM, Wijnands F, Gorecka M, Klop H, Bauerschmidt S, Garritsen A, Koenen HJ, Joosten I, Boots AM, Alkema W | display-authors = 6 | title = Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling | journal = BMC Immunology | volume = 13 | issue = 1 | article-number = 12 | date = March 2012 | pmid = 22413885 | pmc = 3355027 | doi = 10.1186/1471-2172-13-12 | doi-access = free }}</ref>

The patient may develop [[Neutralizing antibody|neutralizing antibodies]] reducing the effectiveness of muromonab-CD3.
Muromonab-CD3 can cause excessive immunosuppression. Although CD3 antibodies act more specifically than polyclonal antibodies, they lower the cell-mediated immunity significantly, predisposing the patient to [[opportunistic infection]]s and malignancies.<ref>{{cite journal | vauthors = Yang H, Parkhouse RM, Wileman T | title = Monoclonal antibodies that identify the CD3 molecules expressed specifically at the surface of porcine gammadelta-T cells | journal = Immunology | volume = 115 | issue = 2 | pages = 189–196 | date = June 2005 | pmid = 15885124 | pmc = 1782146 | doi = 10.1111/j.1365-2567.2005.02137.x }}</ref>

=====IL-2 receptor directed antibodies=====
[[Interleukin-2]] is an important immune system regulator necessary for the clone expansion and survival of activated lymphocytes T. Its effects are mediated by the trimer cell surface [[IL-2 receptor|receptor IL-2a]], consisting of the α, β, and γ chains. The IL-2a (CD25, T-cell activation antigen, TAC) is expressed only by the already-activated T lymphocytes. Therefore, it is of special significance to the selective immunosuppressive treatment, and research has been focused on the development of effective and safe anti-IL-2 antibodies. By the use of [[Recombinant DNA|recombinant gene technology]], the mouse anti-Tac antibodies have been modified, leading to the presentation of two chimeric mouse/human anti-Tac antibodies in the year 1998: [[basiliximab]] (Simulect) and [[daclizumab]] (Zenapax). These drugs act by binding the IL-2a receptor's α chain, preventing the IL-2 induced clonal expansion of activated lymphocytes and shortening their survival. They are used in the prophylaxis of the acute organ rejection after bilateral [[kidney transplantation]], both being similarly effective and with only few side-effects.{{citation needed|date=January 2023}}

===Drugs acting on immunophilins===
{{Anchor|Calcineurin inhibitors}}

====Ciclosporin====
{{Main|Ciclosporin}}
<!-- THE INTERNATIONAL NONPROPRIETARY NAME IS CICLOSOPRIN, WITH AN I. PLEASE DO NOT CHANGE THIS TO CYCLOSPORIN. THANK YOU. -->

Like [[tacrolimus]], ciclosporin (Novartis' Sandimmune) is a [[calcineurin]] inhibitor (CNI). It has been in use since 1983 and is one of the most widely used immunosuppressive drugs. It is a cyclic fungal peptide, composed of 11 amino acids.

Ciclosporin is thought to bind to the cytosolic protein [[cyclophilin]] (an [[immunophilin]]) of immunocompetent lymphocytes, especially [[T-lymphocytes]]. This complex of ciclosporin and cyclophilin inhibits the phosphatase [[calcineurin]], which under normal circumstances induces the transcription of [[interleukin-2]]. The drug also inhibits [[lymphokine]] production and [[interleukin]] release, leading to a reduced function of effector T-cells.

Ciclosporin is used in the treatment of acute rejection reactions, but has been increasingly substituted with newer, and less [[nephrotoxic]],<ref name="pmid19218475 ">{{cite journal | vauthors = Naesens M, Kuypers DR, Sarwal M | title = Calcineurin inhibitor nephrotoxicity | journal = Clinical Journal of the American Society of Nephrology | volume = 4 | issue = 2 | pages = 481–508 | date = February 2009 | pmid = 19218475 | doi = 10.2215/CJN.04800908 | doi-access = free }}</ref> immunosuppressants.

Calcineurin inhibitors and azathioprine have been linked with post-transplant malignancies and [[skin cancer]]s in organ transplant recipients. [[Non-melanoma skin cancer]] (NMSC) after kidney transplantation is common and can result in significant morbidity and mortality. The results of several studies suggest that calcineurin inhibitors have oncogenic properties mainly linked to the production of cytokines that promote tumor growth, metastasis and angiogenesis.

This drug has been reported to reduce the frequency of [[regulatory T cell]]s (T-Reg) and after converting from a CNI monotherapy to a [[mycophenolate]] monotherapy, patients were found to have increased graft success and T-Reg frequency.<ref>{{cite journal | vauthors = Demirkiran A, Sewgobind VD, van der Weijde J, Kok A, Baan CC, Kwekkeboom J, Tilanus HW, Metselaar HJ, van der Laan LJ | display-authors = 6 | title = Conversion from calcineurin inhibitor to mycophenolate mofetil-based immunosuppression changes the frequency and phenotype of CD4+FOXP3+ regulatory T cells | journal = Transplantation | volume = 87 | issue = 7 | pages = 1062–1068 | date = April 2009 | pmid = 19352129 | doi = 10.1097/tp.0b013e31819d2032 | s2cid = 23118360 | doi-access = free }}</ref>

====Tacrolimus====
{{Main|Tacrolimus}}
Tacrolimus (trade names Prograf, Astagraf XL, Envarsus XR) is a product of the bacterium ''[[Streptomyces tsukubensis]]''. It is a [[macrolide lactone]] and acts by inhibiting [[calcineurin]].

The drug is used primarily in liver and kidney transplantations, although in some clinics it is used in heart, lung, and heart/lung transplantations. It binds to the immunophilin [[FKBP1A]], followed by the binding of the complex to [[calcineurin]] and the inhibition of its [[phosphatase]] activity. In this way, it prevents the cell from transitioning from the G<sub>0</sub> into G<sub>1</sub> phase of the [[cell cycle]]. Tacrolimus is more potent than ciclosporin and has less pronounced side-effects.

====Sirolimus====
{{Main|Sirolimus}}
Sirolimus (rapamycin, trade name Rapamune) is a macrolide lactone, produced by the [[actinomycete]] bacterium ''[[Streptomyces hygroscopicus]]''. It is used to prevent rejection reactions. Although it is a structural analogue of tacrolimus, it acts somewhat differently and has different side-effects.

Contrary to ciclosporin and tacrolimus, drugs that affect the first phase of T lymphocyte activation, sirolimus affects the second phase, namely signal transduction and lymphocyte clonal proliferation. It binds to FKBP1A like tacrolimus, however the complex does not inhibit calcineurin but another protein, [[mTOR]]. Therefore, sirolimus acts synergistically with ciclosporin and, in combination with other immunosuppressants, has few side effects. Also, it indirectly inhibits several T lymphocyte-specific kinases and phosphatases, hence preventing their transition from G<sub>1</sub> to S phase of the cell cycle. In a similar manner, Sirolimus prevents B cell differentiation into plasma cells, reducing production of IgM, IgG, and IgA antibodies.

It is also active against [[tumor]]s that are PI3K/AKT/mTOR-dependent.

====Everolimus====
{{main|Everolimus}}
Everolimus is an analog of sirolimus and also is an mTOR inhibitor.

====Zotarolimus====
{{main|Zotarolimus}}
Zotarolimus is a semi-synthetic derivative of sirolimus used in [[drug-eluting stents]].

===Other drugs===

====Interferons====
{{Main|Interferon}}
IFN-β suppresses the production of Th1 cytokines and the activation of monocytes. It is used to slow down the progression of [[multiple sclerosis]]. IFN-γ is able to trigger lymphocytic [[apoptosis]].

====Opioids====
Prolonged use of [[opioid]]s may cause immunosuppression of both innate and adaptive immunity.<ref name="royloh">{{cite journal | vauthors = Roy S, Loh HH | title = Effects of opioids on the immune system | journal = Neurochemical Research | volume = 21 | issue = 11 | pages = 1375–1386 | date = November 1996 | pmid = 8947928 | doi = 10.1007/BF02532379 | s2cid = 7652574 | author-link2 = Horace Loh }}</ref> Decrease in proliferation as well as immune function has been observed in macrophages, as well as lymphocytes. It is thought that these effects are mediated by opioid receptors expressed on the surface of these immune cells.<ref name="royloh"/>

====TNF binding proteins====
A [[TNF-α]] (tumor necrosis factor-alpha) binding protein is a monoclonal antibody or a circulating [[receptor (proteomics)|receptor]] such as [[infliximab]] (Remicade), [[etanercept]] (Enbrel), or [[adalimumab]] (Humira) that binds to TNF-α, preventing it from inducing the synthesis of IL-1 and IL-6 and the adhesion of lymphocyte-activating molecules. They are used in the treatment of [[rheumatoid arthritis]], [[ankylosing spondylitis]], [[Crohn's disease]], and [[psoriasis]].

These drugs may raise the risk of contracting [[tuberculosis]] or inducing a latent infection to become active. Infliximab and adalimumab have label warnings stating that patients should be evaluated for latent TB infection and treatment should be initiated prior to starting therapy with them.

TNF or the effects of TNF are also suppressed by various natural compounds, including [[curcumin]] (an ingredient in [[turmeric]]) and catechins (in [[green tea]]).

====Mycophenolate====
[[Mycophenolic acid]] acts as a non-competitive, selective, and reversible inhibitor of [[inosine-5′-monophosphate dehydrogenase]] (IMPDH), which is a key enzyme in the ''de novo'' [[guanosine]] nucleotide synthesis. In contrast to other human cell types, lymphocytes B and T are very dependent on this process. Mycophenolate mofetil is used in combination with ciclosporin or tacrolimus in transplant patients.

====Small biological agents====
[[Fingolimod]] is a synthetic immunosuppressant. It increases the expression or changes the function of certain adhesion molecules (α4/β7 [[integrin]]) in lymphocytes, so they accumulate in the [[Lymphatic system|lymphatic tissue]] (lymphatic nodes) and their number in the circulation is diminished. In this respect, it differs from all other known immunosuppressants.

[[Myriocin]] has been reported being 10 to 100 times more potent than [[Ciclosporin]].

==Therapy==
Immunosuppressive drugs are used in [[immunosuppression|immunosuppressive therapy]] to:
* Prevent the [[transplant rejection|rejection]] of [[Organ transplant|transplanted]] organs and tissues (e.g., [[bone marrow]], [[heart]], [[kidney]], [[liver]])
* Treat [[autoimmunity|autoimmune diseases]] or diseases that are most likely of autoimmune origin (e.g., [[rheumatoid arthritis]], [[multiple sclerosis]], [[myasthenia gravis]], [[psoriasis]] and [[psoriatic arthritis]], [[vitiligo]], [[granulomatosis with polyangiitis]], [[systemic lupus erythematosus]], [[systemic sclerosis]], [[scleroderma]], [[sarcoidosis]], [[focal segmental glomerulosclerosis]], [[Crohn's disease]], [[Behcet's Disease]], [[pemphigus]], [[ankylosing spondylitis]], and [[ulcerative colitis]]).
* Treat some other non-autoimmune inflammatory diseases (e.g., long term allergic [[asthma]] control).

==Side effects==
A common [[Adverse effect (medicine)|side-effect]] of many immunosuppressive drugs is [[immunodeficiency]], because the majority of them act non-selectively, resulting in increased susceptibility to [[infection]]s, decreased [[cancer immunosurveillance]] and decreased ability to produce antibodies after [[vaccination]].<ref>{{cite journal | vauthors = Lee AR, Wong SY, Chai LY, Lee SC, Lee MX, Muthiah MD, Tay SH, Teo CB, Tan BK, Chan YH, Sundar R, Soon YY | display-authors = 6 | title = Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis | journal = BMJ | volume = 376 | article-number = e068632 | date = March 2022 | pmid = 35236664 | pmc = 8889026 | doi = 10.1136/bmj-2021-068632 }}</ref><ref>{{cite journal | vauthors = Zbinden D, Manuel O | title = Influenza vaccination in immunocompromised patients: efficacy and safety | journal = Immunotherapy | volume = 6 | issue = 2 | pages = 131–139 | date = February 2014 | pmid = 24491087 | doi = 10.2217/imt.13.171 }}</ref>
However, the vaccination status of patients taking immunosuppressive drugs for chronic diseases such as [[Rheumatoid arthritis]] or [[Inflammatory bowel disease]] should be investigated before starting any treatment, and patients should eventually be vaccinated against [[Vaccine-preventable disease]].<ref>{{cite journal |vauthors=Kucharzik T, Ellul P, Greuter T, Rahier JF, Verstockt B, Abreu C, Albuquerque A, Allocca M, Esteve M, Farraye FA, Gordon H, Karmiris K, Kopylov U, Kirchgesner J, MacMahon E, Magro F, Maaser C, de Ridder L, Taxonera C, Toruner M, Tremblay L, Scharl M, Viget N, Zabana Y, Vavricka S |title=ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease |journal=J Crohns Colitis |volume=15 |issue=6 |pages=879–913 |date=June 2021 |pmid=33730753 |doi=10.1093/ecco-jcc/jjab052 |hdl=2078.1/245437 |hdl-access=free }}{{Expression of Concern|doi=10.1093/ecco-jcc/jjab227|pmid=35073579|http://retractionwatch.com/2022/01/25/court-injunction-forces-gastro-journal-to-slap-expressions-of-concern-on-40-articles-about-probiotics/ ''Retraction Watch''}}.</ref> Some studies showed a low vaccination rate against some [[Vaccine-preventable disease]] among patients taking immunosuppressive drugs, despite a generally positive attitude towards vaccinations.<ref>{{cite journal |vauthors=Costantino A, Michelon M, Noviello D, Macaluso FS, Leone S, Bonaccorso N, Costantino C, Vecchi M, Caprioli F |title=Attitudes towards Vaccinations in a National Italian Cohort of Patients with Inflammatory Bowel Disease |journal=Vaccines |volume=11 |issue=10 |page=1591 |date=October 2023 |pmid=37896993 |pmc=10611209 |doi=10.3390/vaccines11101591 |doi-access=free}}</ref>

There are also other side-effects, such as [[arterial hypertension|hypertension]], [[dyslipidemia]], [[hyperglycemia]], [[peptic ulcer]]s, [[lipodystrophy]], [[moon face]], [[Hepatotoxicity|liver injury]] and [[Nephrotoxicity|kidney injury]]. The immunosuppressive drugs also interact with other medicines and affect their [[metabolism]] and action. Actual or suspected immunosuppressive agents can be evaluated in terms of their effects on [[lymphocyte]] subpopulations in tissues using [[immunohistochemistry]].<ref>{{cite journal | vauthors = Gillett NA, Chan C | title = Applications of immunohistochemistry in the evaluation of immunosuppressive agents | journal = Human & Experimental Toxicology | volume = 19 | issue = 4 | pages = 251–254 | date = April 2000 | pmid = 10918517 | doi = 10.1191/096032700678815819 | bibcode = 2000HETox..19..251G | s2cid = 31374180 }}</ref>

== See also ==
* [[Immunosuppression]]
* [[BK virus]]
* [[Behcet's Disease]]
* [[Discovery and development of mTOR inhibitors]]
* [[Transplant rejection#Rejection treatment|Treatment methods for preventing organ rejection]]

== References ==
{{reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Gummert JF, Ikonen T, Morris RE | title = Newer immunosuppressive drugs: a review | journal = Journal of the American Society of Nephrology | volume = 10 | issue = 6 | pages = 1366–1380 | date = June 1999 | pmid = 10361877 | doi = 10.1681/ASN.V1061366 | doi-access = free }}
* {{cite journal | vauthors = Armstrong VW |title=Principles and Practice of Monitoring Immunosuppressive Drugs |journal=LaboratoriumsMedizin |date=February 2002 |volume=26 |issue=1–2 |pages=27–36 |doi=10.1515/LabMed.2002.005 |s2cid=79514959 |doi-access=free }}
{{refend}}

== External links ==
* {{cite web | url = http://pancreas-kidney.com/drugs.html | archive-url = https://web.archive.org/web/20131029140924/http://pancreas-kidney.com/drugs.html | archive-date = 29 October 2013 | title = Pancreas-Kidney Transplantation: Drugs | work = pancreas-kidney.com }} a brief history of immunosuppressive drugs. Retrieved 21 August 2005.
* {{cite web | vauthors = Papich M | url = http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00192.htm | archive-url = https://web.archive.org/web/20161130021827/http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00192.htm | archive-date = 30 November 2016 | work = World Small Animal Veterinary Association (WSAVA) | date = 2001 | title = Immunosuppressive drug therapy | access-date = 21 August 2005 }}
* {{cite web | url = http://www.hivandhepatitis.com/recent/immunology/031204.htm  | archive-url = https://web.archive.org/web/20190228052830/http://www.hivandhepatitis.com/recent/immunology/031204.htm | archive-date = 28 February 2019 | title = Are Immunosuppressive Drugs a Useful Adjuvant to Treatment of HIV with Antiretrovirals? | work = Hivandhepatitis.com | access-date = 21 August 2005 }}
* {{EMedicine|article|430449|Induction of Tolerance}}
* {{cite web | url = https://www.kidney.org/atoz/content/immuno | title = Immunosuppressants | publisher = National Kidney Foundation | work = A to Z Health Guide | date = 24 December 2015 }}
* {{cite web | url = http://www.drugguide.com/ddo/index/Davis-Drug-Guide/Therapeutic_Index/immunosuppressants | title = Immunosuppressants, Pharmacologic profile | work = Drugguide.com | access-date = 15 March 2016 }}
* {{MeshName|Immunosuppressive+Agents}}

{{Major Drug Groups}}
{{Immunosuppressants}}
{{Organ transplantation}}

{{Authority control}}

{{DEFAULTSORT:Immunosuppressive Drug}}
[[Category:Immunosuppressants| ]]
[[Category:Transplantation medicine]]
[[Category:Organ transplantation]]