{"id":583,"date":"2020-02-16T22:12:13","date_gmt":"2020-02-16T16:42:13","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=583"},"modified":"2020-02-16T22:12:13","modified_gmt":"2020-02-16T16:42:13","slug":"immunomodulators","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/immunomodulators\/","title":{"rendered":"Immunomodulators"},"content":{"rendered":"\n<p><strong>Immunomodulators<\/strong><\/p>\n\n\n\n<ul><li>Immunity is usually defined as a state of relative resistance to an infection.<\/li><li>Components of immune system:<ul><li>Lymphocytes<\/li><\/ul><ul><li>Cellular immunity<\/li><\/ul><ul><li>Humoral immunity<\/li><\/ul><ul><li>Immunoglobulin<\/li><\/ul><ul><li>Lymph nodes<\/li><\/ul><ul><li>Spleen<\/li><\/ul><ul><li>Thymus<\/li><\/ul><\/li><\/ul>\n\n\n\n<ul><li>There are 2 types of immunity:<ul><li>Active immunity.<\/li><\/ul><ul><li>Passive immunity.<\/li><\/ul><\/li><\/ul>\n\n\n\n<p>The important components of immune system include:<\/p>\n\n\n\n<ul><li>Granulocytes<\/li><li>Complement synthesis &amp; antibody formation<\/li><li>Cellular immunity<\/li><li>Mucocutaneous barriers<\/li><\/ul>\n\n\n\n<p><strong>Mechanisms of immunomodulation<\/strong><\/p>\n\n\n\n<ul><li>Drugs may modulate immune mechanism by <strong>either suppressing or by stimulating<\/strong> one or more of the following steps:<ul><li>Antigen recognition &amp; phagocytosis<\/li><\/ul><ul><li>Lymphocyte proliferation\/differentiation<\/li><\/ul><ul><li>Synthesis of antibodies<\/li><\/ul><ul><li>Ag \u2013Ab interaction<\/li><\/ul><ul><li>Release of mediators due to immune response<\/li><\/ul><ul><li>Modification of target tissue response<\/li><\/ul><\/li><li>The importance of immune system in protecting the body against harmful molecules is well recognized<\/li><li>However, in some instances, this protection can result in serious problems<\/li><li>E.g, the introduction of allograft can elicit a damaging immune response causing rejection of the transplanted tissue<\/li><li>Benefits of immunomodulators stem from their ability to stimulate natural &amp; adaptive defence mechanisms, such as cytokines, which enables the body to help itself<\/li><li>Natural immunomodulators act to strengthen weak immune systems &amp; to moderate immune systems that are overactive<\/li><li>Plant sterols &amp; sterolins are natural immunomodulators found in some raw fruits &amp; vegetables &amp; in the alga, spirulina<\/li><\/ul>\n\n\n\n<ul><li><strong>Immunomodulators<\/strong>: \u201cThese are the drugs which alters the immune system in a way such as to suppress it (immunosuppressants ) or enhance it (immunostimulants).<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong>Phases of immune response<\/strong><\/td><td><strong>Suppressants<\/strong><\/td><td><strong>Enhancers<\/strong><\/td><\/tr><tr><td>Antigen recognition &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&amp; processing<\/td><td>Corticosteroids Cyclophosphamide<\/td><td>BCG vaccine Tetramisole<\/td><\/tr><tr><td>Amplification<\/td><td>L- Asparaginase Corticosteroids Cyclophosphamide 5-fluorouracil<\/td><td>Concanavalin A Tetramisole<\/td><\/tr><tr><td>Antibody formation<\/td><td>Corticosteroids Cyclophosphamide Cyclosporin A<\/td><td>Lipopolysaccaride Tetramisole<\/td><\/tr><tr><td>Immune affector response &nbsp;<\/td><td>Corticosteroids Cylcophosphamide Cyclosporin A Methotrexate<\/td><td>Tetramisole &nbsp;<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><strong>Immunomodulators types<\/strong><\/p>\n\n\n\n<ul><li>All drugs which modify immune response generally categorized as immunomodulators. These can either function as:<ul><li>1. Immunosuppressants<\/li><\/ul><ul><li>2. Immunostimulants<\/li><\/ul><\/li><li>Some of these can have both the properties depending on which component of immune response they affect<\/li><\/ul>\n\n\n\n<p><strong>Immunosuppressants<\/strong><\/p>\n\n\n\n<ul><li>Glucocorticoids<\/li><li>Calcineurin inhibitors<ul><li>Cyclosporine<\/li><\/ul><ul><li>Tacrolimus<\/li><\/ul><\/li><li>Antiproliferative \/ antimetabolic agents<ul><li>Sirolimus<\/li><\/ul><ul><li>Everolimus<\/li><\/ul><ul><li>Azathioprine<\/li><\/ul><ul><li>Mycophenolate Mofetil<\/li><\/ul><ul><li>Others \u2013 methotrexate, cyclophosphamide, thalidomide &amp; chlorambucil<\/li><\/ul><\/li><\/ul>\n\n\n\n<ul><li>Antibodies<ul><li>Anti-thymocyte globulin<\/li><\/ul><ul><li>Anti CD3 monoclonal antibody<ul><li>Muromonab<\/li><\/ul><\/li><\/ul><ul><li>Anti IL-2 receptor antibody \u2013<ul><li>Daclizumab, basiliximab<\/li><\/ul><\/li><\/ul><ul><li>Anti TNF alpha \u2013 infliximab, etanercept, Adalimumab.<\/li><\/ul><\/li><\/ul>\n\n\n\n<ul><li>Immunosuppressants are the drugs which inhibit cellular\/humoral or both types of immune responses, &amp; have their major use in organ transplantation &amp; autoimmune disease<\/li><li>Problems arising \u2013 Life-long use<\/li><\/ul>\n\n\n\n<p>&nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Infection, cancers<\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp;&nbsp; Nephrotoxicity<\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp; &nbsp;&nbsp;Diabetogenic<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"702\" height=\"540\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-184.png?w=702\" alt=\"\" class=\"wp-image-584\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-184.png 702w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-184-300x231.png 300w\" sizes=\"(max-width: 702px) 100vw, 702px\" \/><\/figure>\n\n\n\n<p><strong>Glucocorticoids<\/strong><\/p>\n\n\n\n<ul><li>Induce <strong>redistribution of lymphocytes<\/strong> \u2013 decrease in peripheral blood lymphocyte counts<\/li><li><strong>Down regulation of IL-1, IL-2, IL-3, IL-6<\/strong><\/li><li><strong>Inhibition of T cell proliferation<\/strong><\/li><li>Increase number of RBCs, platelets &amp; neutrophils in circulation<\/li><li><strong>Enhance rate of destruction of lymphoid cells<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Uses<\/strong><\/p>\n\n\n\n<ul><li>Transplant rejection<\/li><li>&nbsp;GVH \u2013 BM transplantation<\/li><li>Autoimmune diseases \u2013 RA, SLE, Hematological conditions<\/li><li>Psoriasis<\/li><li>Inflammatory Bowel Disease, Eye conditions<\/li><\/ul>\n\n\n\n<p><strong>Toxicity<\/strong><\/p>\n\n\n\n<ul><li>Growth retardation<\/li><li>Avascular Necrosis of Bone<\/li><li>Risk of Infection<\/li><li>Poor wound healing<\/li><li>Cataract<\/li><li>Hyperglycemia<\/li><li>Hypertension<\/li><\/ul>\n\n\n\n<p><strong>Calcineurin inhibitors<\/strong><\/p>\n\n\n\n<ul><li>Cyclosporine &amp;Tacrolimus<\/li><li>Most effective immunosuppressive drugs<\/li><li>Target intracellular signaling pathways<\/li><li>Blocks Induction of cytokine genes<\/li><\/ul>\n\n\n\n<p><strong>Cyclosporine<\/strong><\/p>\n\n\n\n<ul><li>Cyclic peptide composed of 11 amino acid<\/li><li>Extracted from a <strong>soil fungus<\/strong><\/li><li>Selectively <strong>inhibits T lymphocyte proliferation<\/strong>, IL-2 &amp; other cytokine production &amp; response of inducer T cells to IL-1, without any effect on suppressor T cells<\/li><li><strong>Lymphocytes are arrested at G<sub>0<\/sub> or G<sub>1<\/sub> phase<\/strong><\/li><li>Binds to the cytosolic protein cyclophilin (immunophilin) of immunocompetent lymphocytes, especially T-lymphocytes<\/li><li>This complex of cyclosporine &amp; cyclophilin inhibit <strong>calcineurin<\/strong>, which, under normal circumstances, is responsible for activating the transcription of IL-2<\/li><li>It also inhibits lymphokine production &amp; IL release, leads to a reduced function of effector T-cells, does not affect cytostatic activity<\/li><\/ul>\n\n\n\n<ul><li><strong>Topical cyclosporine ophthalmic emulsion 0.05%<\/strong><\/li><li>Currently the only pharmacologic treatment that is FDA approved <strong>(2003)<\/strong> specifically for <strong>DED (Dry Eye Disease).<\/strong><\/li><li>Indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.<\/li><li>Inhaled cyclosporine is being investigated for use in lung transplantation.<\/li><\/ul>\n\n\n\n<p><strong>Uses:<\/strong><\/p>\n\n\n\n<ul><li>Prevent rejection of kidney, liver, cardiac, BM &amp; other allogeneic transplants<\/li><li>Can be used alone<\/li><li>More effective when glucocorticoids are also administered<\/li><li>Most active when administered before antigen exposure<\/li><li>Useful in autoimmune disease as well<\/li><li>Alternative to methotrexate for the treatment of severe, active RA<\/li><li>Selectively suppresses CMI<\/li><li>Free of toxic effects on BM &amp; RE system<\/li><li>For induction it is started orally 12 hrs before the transplant &amp; continued for as long as needed<\/li><li>When graft rejection has started, it can be given i.v<\/li><li>Concentrated in RBCs &amp; WBCs<\/li><li>Metabolized in liver excreted in bile<\/li><li>Biphasic t<sup>1<\/sup>\/<sub>2<\/sub>: 4 -6hrs &amp; 12 -18hrs<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"702\" height=\"495\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-185.png?w=702\" alt=\"\" class=\"wp-image-585\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-185.png 702w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-185-300x212.png 300w\" sizes=\"(max-width: 702px) 100vw, 702px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"202\" height=\"145\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-186.png?w=202\" alt=\"\" class=\"wp-image-586\" \/><\/figure>\n\n\n\n<p><strong>Toxicity : Cyclosporine<\/strong><\/p>\n\n\n\n<ul><li>Renal dysfunction<\/li><li>Tremor<\/li><li>Hirsutism<\/li><li>Hypertension<\/li><li>Hyperlipidemia<\/li><li>Gum hyperplasia<\/li><li>Hyperuricemia \u2013 worsens gout<\/li><li>Calcineurin inhibitors + Glucocorticoids = Diabetogenic<\/li><\/ul>\n\n\n\n<p><strong>Tacrolimus (FK506)<\/strong><\/p>\n\n\n\n<ul><li>Chemically different from cyclosporine, newer immunosuppressant<\/li><li>Macrolide that is isolated from soil fungus<\/li><li>Binds to different cytoplasmic immunophilin protein labelled FK506 binding protein(FKBP)<\/li><li>Same MOA, 100 times more potent<\/li><li>Orally as well as i.v infusion<\/li><li>Metabolized by CYP3A4 &amp; excreted in bile &amp; plasma t<sup>1<\/sup>\/<sub>2 <\/sub>is 12hrs<\/li><li>Clinical efficacy as well as toxicity profile are similar to cyclosporine<\/li><\/ul>\n\n\n\n<p><strong>\u00a0<\/strong><\/p>\n\n\n\n<ul><li>Tacrolimus 0.03% and 0.1% ointment \u2013 FDA approved in Dec. 2000.<\/li><li>Pimecrolimus 1% cream \u2013 FDA approved in Dec. 2001.<\/li><li>Indication: second-line therapy&nbsp; for the short-term and non-continuous chronic treatment of moderate to severe atopic dermatitis in non immunocompromised adults and children.<\/li><li>Not to be used in children less than 2 years.<\/li><li>ADR: burning, pruritus, erythema, edema, increased incidence of malignancies.<\/li><\/ul>\n\n\n\n<p>On February 2005, the FDA issued a warning on the potential risk of neoplasms following the topical application of Calcineurin inhibitors<\/p>\n\n\n\n<p><strong>Toxicity \u2013 Tacrolimus<\/strong><\/p>\n\n\n\n<ul><li>Nephrotoxicity<\/li><li>Neurotoxicity-Tremor, headache, motor disturbances, seizures<\/li><li>GI Complaints<\/li><li>Hypertension<\/li><li>Hyperglycemia<\/li><li>Risk of tumors, infections<ul><li>Drug interaction<\/li><\/ul><ul><li>Synergistic nephrotoxicity with cyclosporine<\/li><\/ul><ul><li>CYP3A4<\/li><\/ul><\/li><\/ul>\n\n\n\n<p><strong>Sirolimus<\/strong><\/p>\n\n\n\n<ul><li>Macrolide antibiotic<\/li><li><strong>Binds to same immunoglobulin FKBP as Tacrolimus<\/strong><\/li><li>Sirolimus-FKBP complex <strong>inhibits another kinase called \u2018mammalian target of rapamycin (mTOR<\/strong>) (does not interact with calcineurin)<\/li><li>Leads to proliferation &amp; differentiation of T-cells activated by IL-2<\/li><li>Extensively metabolized mainly by CYP3A4<\/li><li>Elimination primarily by biliary route<\/li><li>T1\/2- approx 60 hours<\/li><\/ul>\n\n\n\n<p>Uses<\/p>\n\n\n\n<ul><li>Prophylaxis of organ transplant rejection along with other drugs (cyclosporin\/tacrolimus)<\/li><\/ul>\n\n\n\n<p>Toxicity<\/p>\n\n\n\n<ul><li>Increase in serum cholesterol, Triglycerides<\/li><li>Anemia<\/li><li>Thrombocytopenia<\/li><li>Hypokalemia<\/li><li>Fever<\/li><li>GI effects<\/li><li>Risk of infection, tumors<\/li><\/ul>\n\n\n\n<p>Sirolimus \u2013 eluting coronary stent<\/p>\n\n\n\n<ul><li>FDA approved in April 2003.<\/li><li>Sirolimus drug-eluting stents have been shown to reduce restenosis without increasing the risk of stent thrombosis in comparison with bare metal stents through their inhibitory actions on vascular smooth muscle cell proliferation.<\/li><\/ul>\n\n\n\n<p><strong>Everolimus<\/strong><\/p>\n\n\n\n<ul><li>Similar to sirolimus in mechanism, clinical efficacy, doses &amp; drug interactions<\/li><li>Better absorbed orally<\/li><li>Shorter half life (approx 40 hours)<\/li><li>Shorter time taken to reach steady state<\/li><li>Similar uses &amp; toxicity<\/li><li><strong>Everolimus-eluting stents have recently become available in the USA and Europe.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Temsirolimus<\/strong><\/p>\n\n\n\n<ul><li>More water-soluble ester of rapamycin.<\/li><li>Available in both i.v. and oral formulations.<\/li><li>S\/Es &#8211;&nbsp; asthenia, mucositis, nausea and cutaneous toxicity.<\/li><li>Approved by FDA in 2007 for advanced Renal Cell Carcinoma (RCC).<\/li><\/ul>\n\n\n\n<p><strong>Azathioprine<\/strong><\/p>\n\n\n\n<ul><li>Purine antimetabolite<\/li><li>Selectively affects differentiation &amp; function of T-cells<\/li><li>Inhibits cytolytic T-lymphocytes, CMI is primarily depressed<\/li><\/ul>\n\n\n\n<p>Uses<\/p>\n\n\n\n<ul><li>Prevention of renal &amp; other graft rejections<\/li><li>Rheumatoid arthritis(lower doses)<\/li><\/ul>\n\n\n\n<p><strong>Toxicity<\/strong><\/p>\n\n\n\n<ul><li>Bone marrow suppression- leukopenia, thrombocytopenia, anemia<\/li><li>Increased susceptibility to infection<\/li><li>Hepatotoxicity<\/li><li>Alopecia<\/li><li>GI toxicity<\/li><li>Drug interaction: Allopurinol<\/li><\/ul>\n\n\n\n<p><strong>Mycophenolate Mofetil<\/strong><\/p>\n\n\n\n<ul><li>Newer immunosupressant<\/li><li>Prodrug of Mycophenolic acid<\/li><li><strong>Inhibits <em>Inosine Monophosphate Dehydrogenase<\/em><\/strong> \u2013 enzyme <strong>in guanine synthesis<\/strong><\/li><li>Inhibits lymphocyte proliferation, antibody production &amp; CMI<\/li><\/ul>\n\n\n\n<p>Uses:<\/p>\n\n\n\n<ul><li>Prophylaxis of renal transplant rejection<\/li><li><strong>Mycophenolate mofetil+ glucocorticoid + sirolimus \u2013 non-nephrotoxic combination utilized in patients developing renal toxicity with cyclosporin\/tacrolimus<\/strong><\/li><\/ul>\n\n\n\n<p>Toxicity<\/p>\n\n\n\n<ul><li>GI, Hematological<\/li><li>Diarrhea, Leucopenia<\/li><li>Risk of Infection(CMV infections)<\/li><\/ul>\n\n\n\n<p><strong>Cyclophosphomide<\/strong><\/p>\n\n\n\n<ul><li>More marked <strong>effect on B cells &amp; humoral immunity<\/strong><\/li><li><strong>Used in BM transplantation<\/strong> in which short course with high dose is given<\/li><li>In other organ transplantations it is employed only as a reserve drug<\/li><li>In RA, it is rarely used<\/li><li>Low doses are occasionally employed for maintenance therapy in pemphigus, SLE &amp; idiopathic thrombocytopenic purpura<\/li><\/ul>\n\n\n\n<p><strong>Methotrexate<\/strong><\/p>\n\n\n\n<ul><li><strong>Folate antagonist,<\/strong> potent immunosupressant<\/li><li>Markedly depresses&nbsp; cytokine production &amp; cellular immunity &amp; has anti-inflammatory property<\/li><li>Used as 1<sup>st<\/sup> line drug in many autoimmune diseases like rapidly progressing RA, severe psoriasis, pemphigus, myasthenia gravis, uveitis, chronic active hepatitis<\/li><li>Low dose as maintenance therapy is relatively well tolerated<\/li><\/ul>\n\n\n\n<p><strong>Fingolimod<\/strong><\/p>\n\n\n\n<ul><li><strong>Sphingosine 1 Phosphate Receptor agonist<\/strong><\/li><li>R<strong>educe recirculation of lymphocytes from lymphatic system to blood &amp; peripheral tissues<\/strong><\/li><li><strong>\u201cLymphocyte homing\u201d<\/strong> \u2013 periphery into lymph node<\/li><li>Protects graft from T-cell-mediated attack&nbsp;<\/li><\/ul>\n\n\n\n<p>Uses<\/p>\n\n\n\n<ul><li>Combination immunosuppression therapy in prevention of acute graft rejection<\/li><\/ul>\n\n\n\n<p><strong>Anti-thymocyte Globulin<\/strong><\/p>\n\n\n\n<ul><li>Polyclonal antibody <strong>purified from horse or rabbits immunized with human thymic lymphocytes<\/strong><\/li><li>Binds to T lymphocytes &amp; depletes them<\/li><li><strong>Potent immunosupressant<\/strong><\/li><\/ul>\n\n\n\n<p>Uses<\/p>\n\n\n\n<ul><li>Induction of immunosuppression \u2013 transplantation<\/li><li><strong>To suppress acute allograft rejection episodes<\/strong><\/li><\/ul>\n\n\n\n<p>Toxicity<\/p>\n\n\n\n<ul><li>Hypersensitivity<\/li><li>Risk of infection, Malignancy<\/li><\/ul>\n\n\n\n<p><strong>Anti-CD3 Monoclonal Antibody<\/strong><\/p>\n\n\n\n<ul><li>Murine monoclonal antibody against the CD3 glycoprotein expressed near to the T cell receptor on helper T cell<\/li><li>Binds to CD3, a component of T-cell receptor complex involved in<ul><li>antigen recognition<\/li><\/ul><ul><li>cell signaling &amp; proliferation<\/li><\/ul><\/li><\/ul>\n\n\n\n<p><strong>Muromonab<\/strong><\/p>\n\n\n\n<p>Antibody treatment \u00e0Rapid internalization of T-cell receptor \u00e0 Rapid T-cell depletion from blood<\/p>\n\n\n\n<p>\u00e0 Prevents subsequent antigen recognition<\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp; Use<\/p>\n\n\n\n<ul><li>Treatment of acute organ transplant rejection<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <strong><u>Toxicity<\/u><\/strong><\/p>\n\n\n\n<ul><li><strong>\u201cCytokine release syndrome\u201d<\/strong><\/li><li>Aseptic meningitis, life threatening pulmonary edema(rare)<\/li><\/ul>\n\n\n\n<p><strong>Anti-IL-2 Receptor Antibodies<\/strong><\/p>\n\n\n\n<ul><li><strong>Daclizumab &amp; Basiliximab<\/strong><\/li><li>Bind to IL-2 receptor with high affinity on surface of activated T cells \u00e0 <strong>Block IL-2 mediated T-cell activation<\/strong><\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Uses<\/p>\n\n\n\n<ul><li>Prophylaxis of Acute organ rejection &amp; maintenance of graft<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Toxicity<\/p>\n\n\n\n<ul><li>Anaphylaxis, Opportunistic Infections<\/li><\/ul>\n\n\n\n<p><strong>Campath-1H (Alemtuzumab)<\/strong><\/p>\n\n\n\n<ul><li>Monoclonal antibody <strong>binds CD52<\/strong> \u2013 expressed on lymphocytes, monocytes, macrophages<\/li><li><strong>Extensive lympholysis \u2013 Prolonged T &amp; B cell depletion<\/strong><\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Uses<\/p>\n\n\n\n<ul><li>CLL, Bone marrow transplantation, Renal transplantation<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Toxicity<\/p>\n\n\n\n<ul><li>Opportunistic infections<\/li><\/ul>\n\n\n\n<p><strong>Anti-TNF Agents<\/strong><\/p>\n\n\n\n<ul><li>TNF \u2013 Cytokine at site of inflammation<ul><li>Infliximab<\/li><\/ul><ul><li>Etanercept<\/li><\/ul><ul><li>Adalimumab<\/li><\/ul><\/li><\/ul>\n\n\n\n<p><strong>Etanercept<\/strong><\/p>\n\n\n\n<ul><li>Fusion protein<\/li><li>Ligand binding portion of Human TNF-\u03b1 receptor fused to Fc portion of human IgG1<\/li><li>Neutralizes both TNF\u03b1 &amp; TNF\u00df<\/li><li>Prevents activation of macrophages &amp; T-cells<\/li><\/ul>\n\n\n\n<p>Uses<\/p>\n\n\n\n<ul><li>Rheumatoid arthritis<\/li><li>Also approved for severe\/refractory ankylosing spondylitis, plaque<\/li><\/ul>\n\n\n\n<p><strong>Infliximab<\/strong><\/p>\n\n\n\n<ul><li>Chimeric monoclonal antibody against TNF\u03b1<\/li><\/ul>\n\n\n\n<p>Uses<\/p>\n\n\n\n<ul><li>Rheumatoid arthritis<\/li><li>Chron\u2019s disease \u2013 fistulae<\/li><li>Psoriasis<\/li><li>Psoriatic arthritis<\/li><li>Ankylosing spondylosis<\/li><\/ul>\n\n\n\n<p>Toxicity<\/p>\n\n\n\n<ul><li>Infusion reaction \u2013 fever, urticaria, hypotension, dyspnoea<\/li><li>Opportunistic infections \u2013 TB, RTI, UTI<\/li><\/ul>\n\n\n\n<p><strong>Immunostimulants<\/strong><\/p>\n\n\n\n<ul><li>Levamisole<\/li><li>Thalidomide<\/li><li>BCG<\/li><li>Recombinant Cytokines<ul><li>Interferons<\/li><\/ul><ul><li>Interleukin-2<\/li><\/ul><\/li><\/ul>\n\n\n\n<p>Immunization<\/p>\n\n\n\n<ul><li>Vaccines<\/li><li>Immune Globulin<\/li><li>Rho (D) Immune Globulin<\/li><\/ul>\n\n\n\n<p><strong>TETRAMISOLE (LEVAMISOLE)<\/strong><\/p>\n\n\n\n<ul><li>An anthelminthic drug.<\/li><li>Levamisole is orally active levo-isomer of tetramisole, <strong>restores depressed T-cell function<\/strong><strong><\/strong><\/li><li>Used as an adjunct in malignancies, aphthous ulcers &amp; recurrent herpes, also used as <strong>disease modifying drug in Rheumatoid Arthritis<\/strong><strong><\/strong><\/li><li>Mainly <strong>acts by raising c-GMP levels<\/strong> through interaction with thymopoietien receptor sites<\/li><li>leads to decrease in metabolic inactivation of c-GMP accompanied with increased breakdown of c-AMP<\/li><li><strong>Increase in c-GMP level induces lymphocyte proliferation &amp; augmentation of chemotactic responses<\/strong><\/li><li>This reflects into <strong>increased antibody production, lymphokine production, increased phagocytosis<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Thalidomide<\/strong><\/p>\n\n\n\n<ul><li>Anxiolytic, antiemetic drug with anti-inflammatory, cytokine modulatory activity<\/li><li><strong>Enhanced T-cell production of cytokines \u2013 IL-2, IFN-<\/strong><strong>\u03b3<\/strong><\/li><li>NK cell-mediated cytotoxicity against tumor cells<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; USE:<\/p>\n\n\n\n<ul><li>Multiple myeloma, ENL<\/li><\/ul>\n\n\n\n<p><strong>Lenalidomide \u2013 FDA approved in 2005.<\/strong><\/p>\n\n\n\n<ul><li>More potent, less toxic.<\/li><li>Indication<\/li><li>Myelodysplastic syndrome with the chromosome 5q31 deletion.<\/li><li>In combination with dexamethasone for the treatment of multiple myeloma patients.<\/li><\/ul>\n\n\n\n<p><strong>Bacillus Calmate Guerin (BCG) Vaccine<\/strong><\/p>\n\n\n\n<ul><li>It is used as immunological enhancer to stimulate intact immune system (i.e. a non-specific immune-enhancer) of the body.<\/li><li>BCG &amp; its methanol extracted residue (MER) contain muramyl dipeptide as an active immunostimulant ingredient<\/li><li><strong>T-lymphocytes are principle target cells<\/strong> for the action of BCG vaccine.<\/li><li>It causes stimulation of macrophage function, phagocytic activity, lysosomal enzyme activity &amp; chemotaxis mechanisms<\/li><li>It induces the production of lymphocyte-activity factor resulting of phase I of immune response.<\/li><li>Because of its activity against tumour antigen it is beneficial in treatment of lung &amp; breast cancer, acute lympholytic&nbsp; &amp; myelogeneous&nbsp; leukaemia.<\/li><li>It is available as unlyophilized, live or killed lyophilized form.<\/li><\/ul>\n\n\n\n<p><strong>Interferons<\/strong><\/p>\n\n\n\n<ul><li>Low molecular weight glycoprotein cytokines produced by host cells in response to viral infections<\/li><li>Immunomodulatory activity<\/li><li>Bind to cell surface receptors \u2013 initiate intracellular events<ul><li>Enzyme induction<\/li><\/ul><ul><li>Inhibition of cell proliferation<\/li><\/ul><ul><li>Affect viral replication<\/li><\/ul><ul><li>Increased Phagocytosis<\/li><\/ul><\/li><\/ul>\n\n\n\n<p><strong>Interferon alfa-2b<\/strong><\/p>\n\n\n\n<ul><li>Hairy cell leukemia<\/li><li>Malignant melanoma<\/li><li>Kaposi sarcoma<\/li><li>Chronic Hepatitis B<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Adverse reactions<\/p>\n\n\n\n<ul><li>Flu-like symptoms \u2013 fever, malaise, headache<\/li><li>CVS- hypotension, Arrhythmia<\/li><li>CNS- depression, altered behavior<\/li><\/ul>\n\n\n\n<p><strong>Interferon gamma-1b<\/strong><\/p>\n\n\n\n<ul><li>Indication<\/li><li>to reduce the frequency and severity of serious infections associated with chronic granulomatous disease.<\/li><li>S\/E &#8211; fever, headache, rash, fatigue, GI distress, anorexia, weight loss, myalgia, and depression.<\/li><\/ul>\n\n\n\n<p><strong>Interferon beta-1a and interferon beta-1b<\/strong><\/p>\n\n\n\n<p>Indication<\/p>\n\n\n\n<ul><li>Treatment of relapsing and relapsing-remitting multiple sclerosis to reduce the frequency of clinical exacerbations.<\/li><li>S\/E &#8211; Flu-like symptoms (fever, chills, myalgia) and injection-site reactions.<strong><\/strong><\/li><\/ul>\n\n\n\n<p><strong>Interleukin-2 (aldesleukin)<\/strong><\/p>\n\n\n\n<ul><li><strong>Human recombinant interleukin-2.<\/strong><\/li><\/ul>\n\n\n\n<ul><li>Proliferation of cellular immunity \u2013 Lymphocytosis, eosinophilia, release of multiple cytokines \u2013 TNF, IL-1, IFN-\u03b3<\/li><li>Promotes differentiation of T-cells<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Uses<\/p>\n\n\n\n<ul><li>Metastatic renal cell carcinoma<\/li><li>Malignant Melanoma<\/li><\/ul>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Toxicity<\/p>\n\n\n\n<ul><li>Flu- like symptoms- fever, headache, fatigue<\/li><li>Hypotension, drowsiness, confusion, loss of appetite<\/li><\/ul>\n\n\n\n<p><strong>Imiquimod<\/strong><\/p>\n\n\n\n<ul><li>Interact with Toll like receptor TLR7 &amp; TLR8 to boost innate immunity, including the secretion of interferons.<\/li><\/ul>\n\n\n\n<p>Approved for the t\/t of certain diseases caused by HPVs<\/p>\n\n\n\n<p><strong>Oprelvekin<\/strong><\/p>\n\n\n\n<ul><li>Recombinant human IL -11.<\/li><li>Prevention of thrombocytopenia in patient receiving highly myelosuppressive chemotherapy.<\/li><li>S\/E \u2013 Fatigue, fluid retention, Atrial fibrillation.<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td>Palivizumab<\/td><td>in RSV infections in children<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><strong>Active immunization<\/strong><\/p>\n\n\n\n<p><strong>Vaccines<\/strong><\/p>\n\n\n\n<ul><li>Impart active immunity<\/li><li>Active immunization more efficacious &amp; longer lasting than passive immunization<\/li><li>Booster doses required at certain intervals<\/li><li>Anticancer vaccines \u2013 immunizing patients with APCs expressing tumor antigen<\/li><\/ul>\n\n\n\n<p><strong>Immune Globulin<\/strong><\/p>\n\n\n\n<p>Indications<\/p>\n\n\n\n<ul><li>Individual is deficient in antibodies \u2013 immunodeficiency<\/li><li>Individual is exposed to an agent, inadequate time for active immunization<ul><li>Rabies<\/li><\/ul><ul><li>Hepatitis B<\/li><\/ul><\/li><li>Nonspecific immunoglobulins<ul><li>Antibody-deficiency disorders<\/li><\/ul><\/li><li>Specific immune globulins<ul><li>High titers of desired antibody<\/li><\/ul><ul><li>Hepatitis B, Rabies, Tetanus<\/li><\/ul><\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"702\" height=\"526\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-187.png?w=702\" alt=\"\" class=\"wp-image-587\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-187.png 702w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-187-300x225.png 300w\" sizes=\"(max-width: 702px) 100vw, 702px\" \/><\/figure>\n\n\n\n<p><strong>Rho (D) Immune Globulin<\/strong><\/p>\n\n\n\n<ul><li>Antibodies against Rh(D) antigen on the surface of RBC<\/li><li>Binds the Rho antigens &amp; does not allow them to induce antibody formation in Rh \u2013ve individuals<\/li><li>Used for prevention of postpartum\/post-abortion formation of antibodies in Rho-D \u2013ve women (Hemolytic disease of newborn)<\/li><li>Given at 28<sup>th<\/sup> week of pregnancy<\/li><\/ul>\n\n\n\n<p><strong>Plants with immunostimulant potential<\/strong><\/p>\n\n\n\n<ul><li><em>Tinospora cordifolia<\/em><\/li><li><em>&nbsp;Asparagus racemosus<\/em><\/li><li><em>&nbsp;Phyllanthus emblica<\/em><\/li><li><em>Withania somnifera<\/em><\/li><li><em>Piper longum<\/em><\/li><li><em>Terminalia chebula<\/em><\/li><li><em>Aloe vera<\/em><\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Immunomodulators Immunity is usually defined as a state of relative resistance to an infection. Components of immune system: Lymphocytes Cellular immunity Humoral immunity Immunoglobulin Lymph nodes Spleen Thymus There are 2 types of immunity: Active immunity. Passive immunity. The important components of immune system include: Granulocytes Complement synthesis &amp; antibody formation Cellular immunity Mucocutaneous barriers[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/583"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=583"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/583\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=583"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=583"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=583"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}