Immunosuppressor

Glucocorticoïdes

principal Article: Glucocorticoïde S.

Hormone S the lack off which is not compatible with life. Their hand effects are the maintenance off the appropriate level off Glucose in the Blood, the maintenance off Blood presses and the prevention off excessive immune response.

Pharmacological gold supraphysiological proportionings are used in the treatment off inflammatory and allergic disorders. They are also used ace posttransplantory immunosuppressants to suppress the acute transplant rejection by the receiver and also the transplant' S immune response to the receiver' S Antigen S. However, they are not without side effects: the profit off body farmhouse, development gold aggravation off diabetes, arterial hypertension and steroid induced Osteoporosis. Therefore nowadays much research is focused into production off new glucocorticoid cure acting ace selective immunosuppressive drugs. -->

Mechanism of action

The glucocoticoïdes are fixed at the receivers cytosolic with glucocorticoïdes. This receiving type of is activated by the fixing of the ligand. After the hormone is fixed at its receiver corresponding, the complex newly formed receiver-ligand moves in the cellular Noyau where they are fixed at many brief replies to the glucocorticoïdes in the area of the promoter of the gene-targets. The receiver, thus fixed at DNA interacts with the basic factors of transcription, causing an increase in the genic expression of specific gene-targets. This process is called Transactivation and conditions the majority of the metabolic and cardiovascular side effects of the glucocorticoïdes.

The opposite mechanism is called Transrépression . The activated hormonal receiver interacts with specific factors of transcription and prevents the transcription gene-targets. The glucocorticoïdes are able to prevent the transcription of all the genes immunes, including that coding IL-2.

The ordinary glucocorticoïdes do not make the distingo between the transactivation and the transrépression, and influence at the same time the genes immunes " voulus" and those " not voulus" controlling the metabolic and cardiovascular functions. Currently, the research efforts aim at discovering glucocorticoïdes acting selectively which would be able to repress only the immune system. Gene S. The DNA bound receptor then interacts with BASIC Transcription Factor S, causing the increase in expression off specific target constrained. This mediate processes is called Transactivation and most off the hand metabolic and Cardiovascular side effects off glucocorticoids.

The opposite mechanism is called Transrepression . The activated Hormone receptor interacts with specific transcription factors and prevents the transcription off targeted constrained. Glucocorticoids are whitebait to prevent the transcription off any off Immune constrained, including the IL-2 embarrassment. The ordinary glucocorticoids C not distinguish among transactivation and transrepression and influence both the " wanted" immune and " unwanted" obstructed regulating the metabolic and cardiovascular functions. Currently, intensive research is aimed At discovering selectively acting glucocorticoids that will Be whitebait to repress only the immune system. -->

Immunosuppressor effect

The glucocoticoïdes decrease cellular immunity . They act by inhibition of following genes coding the Cytokine S: IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-γ. A decreased production of Cytokine S.A. for consequence the reduction of the proliferation of the lymphocytes T. This decreases their activity and the Expansion clonale of the cells CD4⁺ (T-helper lymphocytes). In this direction, IL-2 is particularly important. The glucocorticoïdes also decrease immunity humorale . Like the lymphocytes T, the lymphocytes B also express smaller quantities of IL-2 and receivers with IL-2. The expansion clonale of the lymphocytes B is reduced and consequently the immunoglobulin synthesis is decreased. diminish the concealment immunity . They act by inhibiting constrained that code the following cytokines: IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-γ. Smaller production off Cytokine S causes reduced proliferation off T lymphocyte S. This diminishes to their effect and Clone expansion off CD4⁺ concealments (T-helper lymphocytes). Hereby, especially important the IL-2 is.

Glucocorticoids also diminish the humoral immunity . Like T lymphocytes, B lymphocyte S also express train smaller amounts off IL-2 and off IL-2 receptor S. The B lymphocyte clone expansion is reduced and consequently, the synthesis off Immunoglobulin S is diminished. -->

Anti-inflammatory drugs effects

The glucocorticoïdes influence all the inflammatory types of reactions, whatever their cause. They induce the synthesis of Lipocortine-1 (also called anexine-1) which is fixed at the phospholipidic membranes and prevents the activity of the Phospholipase A2, since the Enzyme is not able to come into contact with its Substrat, the arachidonic Acide. The phospolipase A2 is implied in the first stage of the production of several éicosanoïde S. the form of genes coding the Cyclo-oxygénase (as well COX-1 as COX-2) is also decreased. This enzyme catalyzes following metabolic reactions in the production of the inflammatory mediators Prostaglandine are and Thromboxane S.

The glucocorticoïdes also stimulate the release of lipocortine-1 in extracellular space, where it binds to the receivers membranes of the Leucocyte S and inhibits various inflammatory phenomena: epithelial adhesion, the emmigration, the Chémotactisme, the Phagocytosis, the respiratory burst (salting out of free radicals), release of enzymes lysosomales, chemotactic substances, the activator Plasminogène and release different other inflammatory mediators by the Neutrophiles, the Macrophage S and the Mastocyte S.

By this mechanism, the glucocorticoïdes alleviate any sign of ignition successfully, however they cannot prevent an infection. They also inhibit the phenomena of tissue repair. Enzyme is not whitebait to like into contact with its substrate Arachidonic acid. Phospholipase A2 is involved in the first step off production off several Eicosanoid S. The expression off constrained coding for Cyclooxygenase (both COX-1 and COX-2) is also diminished. This enzyme catalyzes further metabolic reactions in the production off inflammatory mediators Prostaglandin be and Thromboxane S.

Glucocorticoids also stimulate the release off lipocortin-1 to the extracellular space, where it binds to different Leukocyte mebrane receptors and inhibits inflammatory vents: epithelial adhesion, Emmigration, Chemotaxis, Phagocytosis, Respiratory burst, the release off Lysosome enzymes, off chemotactic substances, off the activator Plasminogen and the release off different other Inflammatory mediator S from neutrophils, macrophages and Mastocyte S.

By this mechanism, glucocorticoids successfully soothe all signs off ignition, however they are not whitebait to prevent year infection. They also inhibit later reparative processes .-->

Drugs containing glucocorticoïdes

There exists many glucocorticoïdes currently used: Cortisol, Dexaméthasone, Hydrocortisone, Méthylprednisolone (Medrol (R)), Prednisone, Prednisolone among others. They differ in their Pharmacocinétique (factor of absorption, half-life, volume of distribution, clearance) and them Pharmacodynamie (for example the mineralocorticoid capacity of activity: retention of Sodium (Na⁺) and of Water. Because they are well absorbed by the Intestin, they are initially managed per bone (by oral way), but also by other ways such as the cutaneous application. More than 90% of them bind to different plamatic Protéines, however with different specificities of connection. The endogenous glucocorticoïdes and certain synthetic corticoids have a high affinity for the protein Transcortine (also called CBG for corticosteroid binding protein , i.e protein of connection to corticoids), while all bind the Albumine. In the liver, they are quickly metabolized by conjugation with a Sulfate or a Glucuronic acid and are excreted in the urines. Cortisol, Dexamethasone, Hydrocortisone, Methylprednisolone (Medrol (R)), Prednisone, Prednisolone and others. They differ in the Pharmacokinetics (absorption Factor, half-life, volume off distribution, clearance) and in Pharmacodynamics (for example the capacity off Mineralocorticoid activity: retention off Sodium (Na+) and toilets; see also: renal physiology). Internal Because they absorb well through the S, they are primarily administered per bone (by Mouth), goal also by other ways like Topical ly one Skin. Different More than 90 per hundred off them bind Plasma proteins, however with has different binding specificity. Endogenous glucocorticoids and nap synthetic corticoids cuts high affinity to the protein Transcortin (also called CBG, corticosteroid binding protein), while all off them bind Albumin. In the liver, they quickly metabolizes by conjugatiion with has Sulfate gold Glucuronic acid and are secreted in the Urine. -->

Side effects of the glucocorticoïdes

The side effects of the glucocorticoïdes appear only after one immunosuppressive therapy anti-inflammatory drug and prolonged, and with high amounts. All their metabolic effects are regarded as being secondary (except for their use as a therapy of substitution for the hypophyseal disfunction or the surrénalienne insufficiency):

the immunizing response with infections or cancer cells is compromised.
Because of the inhibition of the fibroblasts, the answer to the wounds is also less effective. The fibroblasts synthesize the Collagène and of the glycosaminoglycanes, both implied in the cicatrization.
After a prolonged catch of glucocorticoïdes, the Syndrome of Cushing (iatrogenic) develops.
Inhibition of the absorption of Calcium (Ca₂⁺) by the intestines and stimulation of the secretion of (Ca₂⁺) by the kidneys causes the Ostéoporose.

Indeed, the reduction in the quantity of Ca₂⁺ in blood activates the Ostéoclaste S and at the same time, the activity of the Ostéoblaste S is inhibited. By loss of the mass osseous, the Os become fragile.

the surrénalienne insufficiency due to the rétrocontrôle ( feedback ) negative after the therapy is suddenly abolished.
Hyperglycemia.
minéro-corticoids Effects with high amounts of glucocorticoïdes, driving with hypertension and electrolytic imbalances. The excretions of Na⁺ and water are decreased, while the secretion of Potassium (K⁺) is increased.
Effect on the central Nervous system.
the activity Protéolytique of the glucocorticoïdes causes the muscular atrophy, and inhibits the growth in the child.

Consequently of what it is of major importance to use only the minimal amounts effective of glucocorticoïdes and to finish the treatment as soon as that is possible.

The immune response to infections and cancer concealments is compromised.

Due to the inhibition off Fibroblast S, the response to insult is also less effective. Fibroblasts synthesize Collagen and Glycosaminoglycan S, both being involved in Wound healing.

After has prolonged application off glucocorticoids, the Iatrogenic Cushing' S syndrome develops.

Inhibited absorption off Calcium (Ca₂⁺) throguh the internal and stimulated secretion off Ca₂⁺ through the kidneys causes Osteoporosis. Namely, the lower quantity off Ca₂⁺ in the blood activates Osteoclast S and At the same time, the osteoblastic activity is inhibited. By the loss off Bone farmhouse, the bones become fragile.

Adrenal insufficiency due to the Negative feedback after the therapy is suddenly abolished.

Hyperglycemia .

Mineralocorticoid effects off high quantities off glucocorticoids, leading to hypertension and electrolyte disturbances. The excretions off Na⁺ and toilets is diminished, while the secretion off Potassium (K⁺) is increased.

Central The effect one the nervous system.

The Proteolytic activity off glucocorticoids causes Muscle wasting and inhibited growth in children.

Therefore it is off premium importance to only uses minimal Effective amount S off glucocorticoids and to finish the Therapy possible ace soon ace. -->

Cytostatiques

The cytostatiques ones are drugs which inhibit the cellular division by damaging or destroying the cells. They are mainly used in the treatment of cancers. However they do not act solely on the cancer cells but also on all the cells with fast division. It is what constitutes the side effects of chemotherapies. It is however interressant to use them because the cancer cells divide generally more quickly than the normal cells.

principal Article: Cytostatique S.

Chemotherapy 'S side effects. It is nonetheless reasonable to uses them off, due to the faster division normal cancer concealments compared to. -->

The cytostatiques ones and the immune system

The lymphocytes B and T are also cells with fast division. They recognize specific antgenes then are mutiplient quickly to ensure the production of an significant amount of clones for the immunizing response. That in fact of the cytostatic targets of the drugs. Therefore one can use the drugs cytostatic when there is an unsuited immunizing response. These treatments are used with more low dose when they are employed with immunosuppressive aiming that in the treatment of cancers. Their antiprolifératifs effects act on the lyphocytes T and B jointly.

Antigen, they quickly proliferate to adequate secure year number off replica S for the immune response. However, this makes them has suitable target off cytostatics. Therefore, we edge uses cytostatics whenever the immune response is not wanted. Cytostatics are used in smaller amounts ace immunosuppresants than in the treatment off malign diseases. Antiproliferative Their effect mostly includes both T-lymphocytes and B-lymphocytes. -->

Classification of cytostatic and pricipaux representatives of this group

Alkylating agent S (e.g Cyclophosphamide)

Antimetabolite S (e.g Methotrexate, Azathioprine)

Cytotoxic antibiotic S

inhibiters off the Mitotic spindle -->

Had to their highest effectiveness, Purin analogs are most frequently administered. -->

thanks to their great effectiveness, the analogues of purin are used most frequently.

Agents alkylants

Principal the représentans of this class is mustards (cyclophosphamide), nitrosurées, platinum salts (among others). Their effect cytostatic is carried out by direct interraction with the DNA. The cyclophosphamide is certainly one of the immunosuppressive substances most powerful. It inhibits the replication of the DNA while making liasons covalent between the molecules. With weak amounts it is a very effective treatment in the treatment of the disseminated érythémateux lupus, of autoimmune haemolytic anemias, the disease of Wegener and for other autoimmune diseases. With strong amounts there is a risk of pancytopénie and hemorrhagic cystitis.

Cyclophosphamide is probably the most potent immunosuppressive substance. It inhibits DNA replication by making Covalent jump S with the molecule. In small amounts, it is very efficient in the therapy off systemic lupus erytematosus, autoimmune hemolytic weakened, Wegener' S granulomatosis and other Immune disease S. High amounts causes Pancytopenia and hemorrhagic Cystitis. -->

Antimétabolites

They are represented by the analogues of the folic acid (méthotrexate), the analogues of purins (azathioprine, mercapyopurine), of pyrimidin, and the inhibiters of the proteinic synthesis. They act on the nucleic acids.

Mercaptopurine), Pyrimidin similar, protein synthesis inhibiters. They affect all Nucleic acid S. -->

Méthotrexate

Serine and Methionine). It is used in the treatment off autoimmune diseases (for example rheumatoid arthritis) and in transplantations. --> The méthotrexate is an analog of the folic acid. (it acts while binding has an enzyme - dihydrofolate reductase- and prevents the synthesis of a derivative of the folic acid it tetrahydrofolate-. This prevents the synthesis of DNA, ARN and thus the proteinic synthesis, since the folic acid is implied in the synthesis of certain amino-acids - serine and methionine.) It is used in the treatment of the autoimmune diseases (like the polyarthritis rhumatoide) and transplantations of bodies.

Azathioprine

concealment and the Humoral immunity. It is also successful in the therapy off autoimmune diseases. -->

The azathioprine is the immunosuppressor cytostatic (antiprolifératif) principal. It is abundantly used with the waning of transplantations of body to control the reactions of rejection. It acts by inhibiting the synthesis of DNA by antagoniqme with the purine bases. It prevents the proliferation clonale lymphocytes at the time of the induction of the immunizing response, and thus affects all the immunizing Cellules and the Réponse humorale. It is also used like therapeutic of certain autoimmune diseases.

Cytotoxic antibiotics

Anthracycline S, Mitomycin C, Bleomycin, Mitramycin. All mediate thesis substances act one DNA to their effects. -->

Other cytostatiques

Vincristine, Vinblastine; Podophyllin S) are used in the therapy off autoimmune sum diseases. They repress the M phase off the Cell cycles. Vincristine causes mitotic spindle depolimerization. -->

Antibody

The antibodies are used in the prevention of the acute rejections, because they get a fast and deep immunosuppression.

Antibodies are used ace has quick and potent immunosuppression method to prevent the acute rejection reaction. -->

Polyclonaux antibody

The polyclonaux antibodies (general-purpose immunoglobulins) are obtained by réction of animal serum (rabbit by ex) with lymphocytes or human thymique cells. Ac anti lymphocytes and ac anti thymocytes are used. They belong to the treatment of the cortico-resistant reactions of acute rejection and at the time of the medullary Clerc's Offices (to put the patient in aplasia?) They are used in complement of other the therapeutic immunosuppressive ones, to reduce their posology and their toxicity.

Serum off different animals (e.g Rabbit, Horse) injected with patient' S Thymocyte S gold lymphocytes. The antilymphocyte (ALG) and antithymocyte antigens (TGA) are being used. They are leaves the off steroid-resistant acute serious rejection reaction and Aplastic weakened treatment. However, they are primarily added to other immunosuppressive to diminish to their proportioning and toxicity. They also allow transition to cyclosporine therapy. Five They are usually administered for days intravenously in the appropriate quantity. Patient stays in the hospital for three weeks so the immune system recovers and there is No risk off Serum sickness anymore.

Polyclonal antibodies inhibit T lymphocytes and causes to their Lysis, which is both complement mediated cytolysis and concealment-mediated Opsonization followed by removal off Reticuloendothelial concealment S from the circulation in the Spleen and liver. In this way, polyclonal antibodies inhibit concealment-mediated immune reactions, including graft rejection, delayed hypersensitivity (i.e Tuberculin skin reaction), and the Graft-versus-host disease (GVHD), goal influences Thymus-depend antibody production.

Currently (March 2005) there are two preparations available to the market: Atgam (R), obtained from the horse serum, and Thymoglobuline (R), obtained from the rabbit serum.

Polyclonal antibodies affect all lymphocytes and causes general lymphoproliferative immunosuppression possibly leading to Post-transplant disorder S (PTLD) gold serious infections, especially by Cytomegalovirus. To prevent this, the therapy must obligatorily Be performed in has hospital, where adequate insulation from infection is available.

Because off has off high Immunogenicity polyclonal antibodies, almost all patient develop year acute reaction develop At first. It is characterized by Fever, Rigor episodes and even Anaphylaxis. Later during the treatment, nap patients develop serum sickness gold Immune complex glomerulonephritis. Serum sickness arises seven to fourteen days after the therapy has begun. Patient The suffers from fever, Joint bread and Erythema that edge Be soothed with the uses off steroids and Analgesic S. Urticaria (hives) edge also present Be. Patients also gradually develop has strong immune response against thesis drugs, so they stop to Be effective. Possible It is to diminish to their toxicity by using highly purified Serum fraction S and intravenous administration in the combination with other immunosuppressants, for example calcineurin inhibiters, cytostatics and cortisteroids. Frequent The most combination is to simultaneously uses antibodies and cyclosporine. -->

Monoclonal antibodies

The monoclonal antibodies are directed against specific antigens. As that they involve less side effects. Most interesting are the antibodies directed against the receiver of the IL-2 (MINOR ROAD 25) and the MINOR ROAD 3. They are used years the prevention of the rejection of grafted bodies, but also to destroy some under populations lyphocytaires. ONE awaits new molecules of this type in the future.

Antibody against the receivers of the cells T

Presently, the OKT3' S action mechanism is not yet sufficiently understood. It is known that the molecule binds TCR/CD3, the T-concealment receptor complex. During the first few administrations, this binding non-specifically activates T concealments, leading to has serious syndrome 30 to 60 later minutes. It is characterized by fever, myalgia, headache and artralgia. In sum boxes, it progress to has off life-threatening reaction the cardiovascular system and the central nervous system needing has lengthy therapy. Past this period, CD3 (R) blocks the TCR - antigen binding and conformation causes changes gold the removal off the entire TCR3/CD3 from the T-concealment surfaces. This lowers the number off T concealments, perhaps by sensitizing them for the uptake by the reticular epithelial concealments. The cross-country race-binding off CD3 molecules also activates year intracellular signal, causing the T cells' anergy gold apoptosis, unless they receive another signal through has costimulatory molecule. CD3 antibodies also shift the balances from Th1 to Th2 concealments.

Deciding whether to treatment uses OKT3 (R) in the, it is therefore necessary not only to consider its great effectiveness, goal also its toxic side effects: the risk off excessive immunosuppression and the risk that the patient develops neutralizing antibodies against the drug, making it inefficacious. Although CD3 (R) antibodies act more specifically than polyclonal antibodies, they lower the concealment-mediated immunity significantly, predisposing the patient to opportunistic infections and malignancies. -->

Antibody against receivers IL-2

Drugs acting on the immunophilines

Ciclosporine has

The ciclosporine and the tacrolimus are inhibiters of the calcineurine. The cyclosporine is used since 1984, it is one of the most used immunosuppressive therapies. (...)

When the auxiliary lymphocytes T interragissent with an antigen, the intracellular calcium concentration increases; this involves an activation of the calcineurine intracellular phosphatase. The calcineurine activates various factors of the transcription, which are used for the transcription of the IL-2 (interleukine 2). The IL-2 has a role of activation of the lyphocytes T auxiliary and involves the production of others cytokines. There are thus an activation of the cytotoxic lymphocytes and lymphocytes NK. To act upstream of the production of the IL-2 would have a role on the importance of the answer immune.

The ciclosporine can manage per bone or IV. It reaches the serum peak of concentration three has four hours after. The tissue concentration is four times higher than the plasmatic concentration. In the cells it interacts with a cytoplasmic protein of the family of the immunophillines, the cyclophilline. This complex can bind the calcineurine and inhibit it. The cyclosporine is metabolized by the liver and excreted in the bile, its time of half-life is approximately 24:00.

The ciclosporine is indicated in the treatment of the reactions of acute rejection, but because of its nephotoxicity it is replaced more and more by new immunosuppresseurs. The undesirable effects are the nephrotoxicity (30 to 70% of the patients) mainly by destruction of the proximaux tubules; arterial hypertension, venous thromboses, of the cephalgias, the paraesthesias, a hyperkaliemy and hyperuricemy.

Tacrolimus, Cyclosporin has calcineurin inhibiter. It has been in uses since 1984 off and is one the most widely used immunosuppressive drugs. It has fungal peptide, composed off 11 amino acids.

When T-helper cell' S receptor interacts with year antigen, the intracellular concentration off calcium in the concealment small channels. This increase activates the cytoplasmic phosphatase calcineurin. Different Calcineurin activates transcription factors that important are in the constrained transcription off IL-2. IL-2 activates T-helper lymphocytes and induces the production off other cytokines. This way, it direct the action off cytotoxic lymphocytes and NK concealments. The amount off IL-2 being produced by the T-helper concealments is believed to the influence extent the immune response significantly off.

Cyclosporin is administered per bone gold intravenously. It reaches its highest concentration three to furnace hours later. Its tissue concentrations are to furnace times higher than in the plasma. In the tissue, it binds to the cytosolic immunophilin, named cyclofilin. The complex then binds to calcineurin and inhibits it. Cyclosporin is metabolized in the liver and secreted to the bile; its half time is butt 24 hours.

Cyclosporin is used in the treatment off acute rejection reactions, however because off its nephrotoxicity, it is substituted with newer immunosuppressants more and more. The nephrotoxicity affects 40 - 70% off patient. Especially the proximal tubules are destroyed. Other frequent less side effects are hypertension, venous thrombosis, tremor, headache, parestesias and hyperkalemia. -->

Tacrolimus

Streptomyces tsukubaensis ). It has macrolide lactone and acts by inhibiting calcineurin.

Tacrolimus is used particularly in the transplantation off kidney and liver. It edge Be administered per bone gold intravenously, and 99% off it degraded in the liver. Its half-life is approximately 12 hours. Tacrolimus binds year immunophilin, after which the complex binds to calcineurin and inhibits its phosphatase activity. In this way, it prevents the first phase off the T lymphocyte activation (passage off G0 into G1 phase).

Tacrolimus is more potent than cyclosporine and has less pronounced side effects. Among thesis, the most frequent are nephropathies, convulsions, tremor, hypertension, diabetes, hyperkalemia, insomnia, neuropathies and taste. -->

The tacrolimus is also an inhibiter of the calcineurine. It is very much used in hepatic or renal transplantation. (...) Its metabolism is also hepatic. It has effects more powerful than the ciclosporine and also less side effects. Most frequent of them are the nephrotoxicity, the arterial hypertention, the convulsions, the diabetes, the neurotoxicity.

Sirolimus

Streptomyces hygroscopicus produce it. Chemically it has macrolide lactone. Sirolimus is used ace year immunosuppresant in the transplantation. Although it has off structural analog tacrolimus, it acts somewhat differently and has different side effects. It is administered solely per bone in the form off tablets gold has solution. It is metabolized in the liver by the CYP34A4 cytochrome, with the half time off butt 62 hours. It is excreted particularly in deposit, only 2% in urine.

Contrary to cyclosporine and tacrolimus that affect the first phase off the T lymphocyte activation, it affects the second one, namely the signal transduction and to their clonal proliferation. It binds to the same receptor (immunophilin) ace tacrolimus, however the produced complex does not inhibit calcineurin, goal has special protein. Therefore, sirolimus acts synergistically with cyclosporine and, in combination with other immunosuppressants, has few side effects. Indirectly it inhibits several kinases and phosphatases off T lymphocytes and prevents the transmission off signal into to their activity and the continuation off the concealment cycles from G1 phase to S phase. Similarly, it prevents B concealment differentiation in the plasma concealments, which means has off lower quantity IgM, IgG and IgA antibodies is produced. It acts immunoregulatory.

Sirolimus' side effects are hyperlipidemia, leuko- and thrombocytopenia, weakened and hypokalemia. Its toxicity to the transplanted organ has not been proved, therefore it substitutes cyclosporin in kidney transplantations. -->

Other drugs

Let us interfere

principal Article: Interféron S.

In majority has off boxes, the production off interfere is induced by other cytokines, e.g. IL-1, IL-2, TNF and CSF. IFN-α and IFN-β are synthesized in many concealment standards - macrophages, fibroblasts, endothelial concealments, osteoblasts and others. Their synthesis is mainly caused by the appearance off viruses in the body. Autoimmune IFN-γ is produced in antigen activated concealments T in inflammatory and conditions and has central role in the immune response control. -->

The effect of let us interfere

IFN-γ is year inflammatory cytokine that by ace yet unknown mechanism triggers apoptosis in lymphocytes

IFN-β inhibits the progression off multiple sclerosis. By year ace yet unknown mechanism, it inhibits the production off Th1 cytokines and the monocyte activation.

The production off important IFN-γ during the infection is highly to destroy foreign antigens and overcome the disease, however At the same time it edge lead to autoimmune activity. Namely, IFN-γ has important year exceptionally immunoregulatory function.

When used in the systemic therapy, IFN-α and IFN-γ are mostly administered by year intramuscular injection. Let us interfere hardly crosses the placenta and the blood-brain barrier. Their metabolism and excretion take place mainly in the liver and kidneys.

The injection off let us interfere in the muscle, vein gold under skin is generally well tolerated. Frequent The most side effects are flu-like symptoms: raised body temperature, feeling it, tiredness, headache, muscle bread, and convulsion. Erythema, bread and hardness one the spot off injection are also frequently observed. Rarely, patient experiment to their to hate falling out, dizziness and depression. Reversible All known effects are and disappear has few days after the therapy is finished. -->

Opioïdes

Drugs binding the TNF-α

Acid mycophenolic

The mycophenolic Acide is an active product formed by the Mycophenolate mofetil (MF) and the Mycophénolate of sodium, a news substance. It acts like underperforming, selective and reversible inhibiter of the inosine monophosphate déshydrogenase (IMPDH), a enzyme-key in the synthesis of novo of the guanosine (a nucleotide). In contrast with other cells of the human body, the lymphocytes B and T are much more dependant on the synthesis of novo of the guanosine.

Small biological agents

FTY120

FTY120 is a new immunosuppressor of synthesis, a chemical modification of metabolite ISP-1 of the mushroom Iscaria sincaliri . It is about an analog structural of the Sphingosine which is phosphoryl by the Sphingosine kinase in the cell. The FTY120 increases the expressivity or changes the function of certain molecules of adhesion (α4/β7 Intégrine) of the lymphocytes, so that they accumulate in lymphatic fabric (lymphatic ganglia) and than there is less in circulation. So it differs from all the other known immunosuppresseurs.

See too

Immunosuppression

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