Immunomodulators PDF

Drugs that modulate immune system IMMUNOMODULATORS Lecture contents: Definition of immunomodulators General immunosuppressant Innate immunosuppressant Adaptive immunosuppressant Immunity boosters Immunomodulaters are drugs that modify immune system activity by either stimulating or suppres...

Drugs that modulate immune system IMMUNOMODULATORS Lecture contents: Definition of immunomodulators General immunosuppressant Innate immunosuppressant Adaptive immunosuppressant Immunity boosters Immunomodulaters are drugs that modify immune system activity by either stimulating or suppressing it. They can target both innate and adaptive immunity by acting on one of the following steps: ✓Antigen recognition and phagocytosis ✓Release of mediators due to immune response ✓Lymphocyte proliferation/differentiation ✓Antibody synthesis ✓Ag-Ab interaction ✓Modification of target tissue response Immunosuppressant Are drugs that inhibit cellular/humoral or both types of immune responses, mainly used in autoimmune diseases and organ transplant. Due to the life-long use of these drugs, nearly they are all sharing the side effects of causing infection, cancers, nephrotoxicity ,etc…. General immunosuppressants Steroids Ex: Prednisone, methylprednisolone, dexamethasone Steroids have broad effects to block inflammation through the following; ▪ Inhibit cytokines that cause inflammation (down regulation of IL-1, IL-2, IL-3, IL-6) ▪ Make it more difficult for immune cells to travel to spots of infection or injury though the body (decrease peripheral blood lymphocyte count) ▪ Inhibit T cell proliferation & enhance destruction of lymphoid cells (T & B cells depletion) ▪ Increase number of RBCs, platelets & neutrophils in circulation while deplete eosinophils Uses: Autoimmune diseases; asthma, RA, SLE Psoriasis IBD Eye conditions Transplant rejection GVH-BM transplantation Side effects: Depending on how much steroids are being taken and for how long many adverse reactions occur ▪ Issues related to bone health (avascular necrosis of bone) ▪ High blood pressure ▪ Hyperglycemia ▪ Cataracts ▪ Risk of infections, including rare types of pneumonia. ▪ Growth retardation and poor wond healing on long-term steroids use caution must be taken before receiving vaccinations to patients Colchicine A plant sourced alkaloid obtained from autum crocus ( Colchicum autumnale) The drug causes suppression of inflammation by accumulating in WBCs affecting their motility, mobilization (chemotaxis) and adhesion. ▪ Inhibits activation and migration of neutrophils to site of action. ▪ Interfere with inflammasome complex in neutrophils and monocytes that mediate IL-1β activation. ▪ Binds tubulin protein thereby inhibiting mitosis (antimitotic). ▪ Interrupts mast cells and lysosome degranulation. ▪ Inhibit release of superoxide anions. Indications : Gout flares Familial mediterranean fever (FMF) Protective against cardiovascular events in coronary atherosclerosis. Other autoinflammatory disorders (pericarditis- off label use). Side effects: ▪ Colchicine can commonly cause diarrhea, stomach pain, nausea and vomiting ▪ Headache and fatigue. ▪ Muscle and nerve problems. ▪ low blood cell counts ▪ Dangerous interactions with other medications ( as it interacts with P- glycoprotein transporter and CYP3A enzyme) and food ( grapefruit juice) ▪ Has a narrow therapeutic index and it is deadly in overdose. Hydroxychloroquine Belongs to disease-modifying antirheumatic drugs (DMARDs) family of medications. MOA: Its general mode of action of Hydroxychloroquine is the interruption of signaling in the immune system, thereby reducing the inflammatory response. It may prevent activation of certain immune cells called dendritic cells ( affecting Ag presenting) Inhibits stimulation of (TLR9) that induces inflammatory responses through activation of innate immunity. Uses: Malaria RA ( certainly during pregnancy) SLE Prophyria cutanea trada Adverse effects: Diarrhea, nausea, vomiting and abdominal pain. Headache and muscle weakness. Rash, vision changes ( may cause retinopathy), heart problems and low blood cell counts. It has many drug interactions (azithromycin, penicillamine, insulin & oral hypoglycemic drugs) ❖ It is not associated with an increased risk for infection. ❖ Patients should have regular eye examinations while taking this medication. Sulfasalazine Belongs to (DMARDs) family of medications Mechanism of action: Being metabolized by intestinal flora into 2 components sulfapyridine & 5-aminosalicylate which are both active and have immunosuppressive, antibacterial and anti-inflammatory effects. Inhibits the formation of prostaglandins. Uses: RA, psoriatic arthritis, ulcerative colitis, Crohn’s disease and other autoinflammatory conditions Adverse effects: Nausea, headache, severe cutaneous reactions. should be avoided in patients allergic to sulfa antibiotics or salicylates and used with caution in patients with G6PD deficiency. ❑ Patients should use sun protection when taking this medication. ❑ It may temporarily reduce sperm counts and cause orange urine. Dapsone Originally is an antibiotic commonly used with rifampcin and clofazimine for treatment of leprosy plus other types of infections however it has considerable use in autoimmune diseases; dermatitis herpetiformis, cutaneous LE, chronic spontaneous urticarial, and other autoimmune conditions Mode of action: as anti-inflammatory it prevents cellular injury from free radicals, and inhibits leukotrienes or prostaglandins. Adverse effects: Gastrointestinal upset, rash, and headache. Blurred vision. Less commonly it may cause mood changes, muscle weakness, low blood cell counts, fast HR and shortness of breath. ❖ It should be used with caution in patients with G6PD deficiency and avoided in patients with a sulfa-allergy. Methotrexate; MTX Is an antimetabolite and DMARD agent used to treat ; Rheumatoid arthritis, psoriasis , ectopic pregnancies and certain cancers Mode of action: it competitively inhibits (DHFR) enzyme interrupting the use of folic acid thereby inhibiting DNA, RNA & protein synthesis. This is a key part of making DNA and RNA that are important for T cells and B cells to grow, divide, and survive. Inhibits T cells activation and causes down regulation of B cells Inhibits binding of IL-1β to its surface receptors. Adverse effects: Increased susceptibility to bacterial and viral infections Hepatotoxicity, allergic reactions, leukopenia and kidney failure MTX has serious interactions with penicillins, probencid, NSAIDs, PPIs and retinoids. ❖ viral infections such as hepatitis B and C, as well as RFT and LFT must be checked before & during the use of this drug. ❖ Patients are often prescribed folic acid to reduce the side effects of this medication, such as mouth sores, diarrhea or nausea. Mycophenolate Mofetil / Sodium is an immunosuppressive drug mainly used to prevent organ rejection in solid organ transplantation and to treat autoimmune diseases e.g Crohn’s disease & LE. Mode of action: It blocks Inosine-5′-monophosphate dehydrogenase (IMPDH) enzyme which is important for making DNA and RNA in lymphocytes thereby controlling immune responses in autoimmune conditions. Adverse effects: increased risk of infections Nausea, vomiting, dirrhea & GIT bleeding Leukopenia & anemia Hyperglycemia and hypercholesterolemia. Pulmonary fibrosis and neoplasia. ❖ viral infections such as hepatitis B and C must be checked before starting this medication. ❖ Live vaccines should be avoided. Azathioprine is an immunosuppressive drug used either alone or in combination to treat many autoimmune diseases e.g RA, IBDs , myasthenia gravis & atopic dermatitis. Also used in prevention of transplant rejection. Mechanism of action: The drug is a purine synthesis inhibitor, as it is converted within tissues to 6-MP & 6- Thioguanine which are false building blocks for DNA & RNA thereby stopping nucleic acids from being made correctly. Adverse effects: high risk of infections Nausea & vomiting, rashes Bone marrow suppression and acute pancreatitis. It may increase the risk for malignancy ❖ A genetic test for protein called thiopurine S- methyltransferase (TPMT) may be done before starting this medication to make sure the patient’s ability to metabolize the drug Leflunomide Is an immunosuppressive (DMARD). Used in: Active RA, psoriatic arthritis and organ rejection. MOA: It is a pyrimidine synthesis inhibitor that acts by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), which plays a key role in the de novo synthesis of uridine monophosphate (rUMP) required for the synthesis of DNA and RNA. Hence, leflunomide inhibits the reproduction of rapidly dividing cells, especially lymphocytes. also inhibits several tyrosine kinases. Side effects: Diarrhea, UT and RT infections Nausea, vomiting and abdominal pain Allergic reaction rash and eczema Chest pain and shortness of breath. Innate immunity modulators Anti-IL-1 Biologics: ❑ IL-1 family is a group of 11 cytokines, which induces a complex network of proinflammatory cytokines that play an important role in the innate immune responses of the body against infection as well as regulating and initiating inflammatory responses. ❑ IL-1α and IL-1β are the most distinct members, as they possess strong proinflammatory effect. ❑ They have a natural antagonist IL-1Ra (IL-1 receptor antagonist) which regulates IL-1α and IL- 1β activity by competing with them for binding sites of the receptors IL-1R1 & IL-1R2. ❑ IL-1 are intensely produced by tissue macrophages, monocytes, fibroblasts, DCs, also by B cells, NK cells, and epithelial cells. These cytokines increase the expression of adhesion factors on endothelial cells to enable transmigration of immunocompetent cells, such as phagocytes, lymphocytes and others, to sites of infection. ❑ They also affect the activity of the thermoregulatory center in hypothalamus, which leads to a rise in body temperature (fever) That is why IL-1 is called an endogenous pyrogen. ❑ Besides, IL-1 also cause hyperalgesia (increased pain sensitivity), vasodilation and hypotension Mode of actions: ❑Anakinra : is a recombinant form of the IL-1 receptor antagonist (IL-1RA) that blocks IL-1α & IL-1β from binding to IL-1 receptors ❑ Canakinumab : is a human monoclonal antibody that bind IL-1β specifically preventing its receptor interaction ❑ Rilonacept: soluble receptor that neutralizes IL-1β (predominantly) and IL-1α The result is reduction in fever and overall inflammation. Use: Familial Mediterranean fever, Systemic Juvenile Idiopathic Arthritis , RA , gout flares & etc….. Adverse reactions: Increased risk of infection ; upper RTIs and UTIs Injection site reactions, headaches & increased cholesterol levels. Decreased white blood cells, or decreased platelets ❖ A test for tuberculosis infection is recommended before starting these drugs. ❖ Avoiding live vaccines while on these medications. ❖White blood cell count is often monitored while taking these medications. Tumor necrosis factor (TNF,TNF-α) Is a cytokine used by the immune system for cell signaling. If macrophages detect an infection, they release TNF to alert other immune system cells as part of an inflammatory response. TNF signaling occurs through two receptors: TNFR1 and TNFR2. TNFR1 is expressed on most cell types, whereas TNFR2 is restricted primarily to endothelial, epithelial, and subsets of immune cells. TNFR1 signaling tends to be pro-inflammatory and apoptotic, whereas TNFR2 signaling is anti-inflammatory and promotes cell proliferation.  TNF is produced by macrophages, lymphoid cells, mast cells, endothelial cells, and other types of cells, Large amounts of TNF and IL-1 are released in response to bacterial products e.g lipopolysaccharide. It has a number of actions on immune system, generally together with IL-1 and IL-6: ❑ On the hypothalamus: they affect thermoregulatory center causing Fever ❑ On the liver : stimulating the acute phase response, leading to an increase in C-reactive protein and a number of other mediators. ❑ It is a potent chemoattractant for neutrophils, and induce their migration. ❑ On macrophages: stimulates phagocytosis, and production of IL-1 and prostaglandin E2 (PGE2). Anti-TNF Biologics (TNF Inhibitors) They are either monoclonal antibodies e.g Infliximab , Adalimumab , Golimumab & Certolizumab that inhibit TNF-α from binding to receptors, or fusion protein e.g Etanercept that acts as a decoy receptor for TNF. Use: RA, psoriasis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis Adverse reactions: higher risk of serious infections. CHF, demyelinating disease, a lupus-like syndrome & injection site reactions. long-term risk of cancers such as lymphoma ❖Testing for tuberculosis, hepatitis B and C, HIV, any risk of fungal infection must be done before initiating the medication. ❖ live vaccines should be avoided when taking this family of medications. Natural anti-TNF agents: ❖ Curcumin (a compound present in turmeric),Catechins (in green tea) and Cannabidiol also seem to have anti-inflammatory properties through inhibition of TNF-α production ❖ 5-HT2A receptor agonists have also been shown to have potent inhibitory effects on TNF-α, including Psilocybin found in many species of mushrooms. ❖ Thymoquinone, a compound found in the flower Nigella sativa, has been studied for possible TNF-α inhibition and related benefits for autoimmune disorder treatment. Anti-IL-6 Biologics IL-6 is a cytokine produced by Monocytes, Macrophages , lymphocytes & fibroblasts. it is an important mediator of fever and of the acute phase response, as well as the production of neutrophils, supporting growth of B cells and antagonizing the regulatory T cells. IL-6 inhibitors are monoclonal antibodies e.g Tocilizumab that blocks IL-6 receptors & Sarilumab that targets IL-6 itself. Indications for use: RA, giant cell arteritis, juvenile idiopathic arthritis Adverse reactions: Higher risk of infections. Rashes Transient elevation in liver enzymes. Rarely neutropenia and thrombocytopenia. Complement blockers. Eculizumab: is a monoclonal Ab that targets terminal complement component 5 C5; inhibits its cleavage by the C5 convertase into C5a which is a potent anaphylatoxin with prothrombotic and proinflammatory properties, and C5b, which then forms the terminal complement complex C5b-9 and also has prothrombotic and proinflammatory effects. use: Paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (a-HUS) Adverse reactions: Increased risk of infections caused by Neisseria (family of bacteria that causes gonorrhea and meningococcal meningitis). Headaches & severe anemia. Increased risk of infections (pneumonia, upper RTIs, colds & UTIs) loss of white blood cells anaphylactic & hypersensitivity reaction a sense of tingling or numbness, blurred vision, vertigo, ringing in the ears & many many others. ❖ vaccination against meningococcus is a must before starting this drug and taking antibiotics to prevent infections is also considered. Adaptive immunity modulators Anti-CD20 = Rituximab Is a monoclonal antibody that works by binding to the CD20 protein which is a surface protein that is expressed chiefly on B cells triggering cell death. CD20 has no known function or natural ligand, however it’s thought to act as calcium channel , helping to maintain intracellular calcium and hence cell function. ❖ The diseases that are treated with rituximab all require B cells to either grow (such as lymphoma) or make antibodies that bind to certain parts of our body and cause inflammation (such as RA and autoimmune skin disease). Indications for use: Non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, RA, MG, vasculitis & autoimmune skin disease Adverse reactions: A higher risk of diseases that are normally cleared by antibodies, e.g infections in the sinuses and lungs. Re-activation of hepatitis B in previously diseased patients , so pre HB testing is required. Rash, itchiness, low blood pressure, shortness of breath & cardiac arrest. Increased risk of viral infections such as herpes. ❖ The response to vaccines is also limited after rituximab and all indicated vaccinations should be given before its use. ❖ In most people who get rituximab, the B cells return within one year, However, in a subset of individuals treated with rituximab, B cells do not return and they may have low antibody levels for many years or lifelong. B Cell Growth Factor Targeting Biologics: Belimumab (Benlysta) Is a monoclonal antibody that Binds BLyS (B lymphocyte stimulator, also called BAFF) which is a cytokine produced by monocytes , macrophages & other cell types that plays important role in B cell survival and growth. Indications for use: Systemic lupus erythematosus (SLE) adverse reactions: higher risk of skin infections and pneumonia are the most common infections. Nausea & diarrhea Infusion site & hypersensitivity reactions ❖ Live vaccines should be avoided when taking belimumab. Calcineurin inhibitors: Calcineurin (CaN) is a calcium dependent serine/threonine protein phosphatase that activates T cells. When an antigen-presenting cell interacts with a T cells, there is an increase in the cytoplasmic level of calcium, which activates calcineurin. Calcineurin induces indirectly the transcription of IL-2 genes. IL-2 has essential roles in key functions of the immune system, tolerance and immunity, primarily via its direct effects on T cells : In the thymus, where T cells mature, it prevents autoimmune diseases by promoting the differentiation of certain immature T cells to regulatory T cells, which suppress other T cells that are otherwise primed to attack normal healthy cells in the body. IL-2 enhances activation-induced cell death (AICD). IL-2 also promotes the differentiation and activation of T cells into effector T cells and into memory T cells when the initial T cell is also stimulated by an antigen, thus helping the body fight off infections. IL-2 increases the cell killing activity of both NK cells and cytotoxic T cells. A- Cyclosporine Is a natural product obtained from a fungus that is used orally or I.V as immunosuppressant. Mode of action: It acts by decreasing T lymphocyte functions and production of inflammatory cytokines through inhibition of Calcineurin. Indications for use: Prevent organ transplant rejection, graft versus host disease, RA, psoriasis, chronic urticaria as eye drops for keratoconjunctivitis sicca (dry eyes). Adverse effects: High risk for infections. Headache, vomiting, high blood pressure and decreased kidney function. It may increase the risk for malignancy. ❖ all live vaccines must be avoided when taking this medication. B-Tacrolimus , Sirolimus, Pimecrolimus It is a macrolide lactone obtained from Streptomyces fermentation to broth of Japanese soil. it acts as immunosuppressive drug through inhibition of Calcinurine. Uses: prevent organ transplant rejection. topical medication in the treatment of T-cell-mediated diseases such as eczema ,psoriasis, and vitiligo. Side effects : Infection, cardiac damage, hypertension, blurred vision, liver and kidney problems. Hyperkalemia, hypomagnesemia, hyperglycemia, DM, lung damage. Neuropsychiatric problems such as loss of appetite, insomnia,, confusion, weakness, depression, neuropathy, seizures & tremors. An increased risk of malignancy. Increased sensitivity to sunlight and itching. Monoclonal Antibodies (mAbs) A monoclonal antibody is an antibody produced from a cell line made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies can have monovalent affinity, binding only to the same epitope. In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different antibody-secreting plasma cell lineages. Monoclonal antibodies are being used on a clinical level for both the diagnosis and therapy of several diseases. T Cell Co-stimulation and Activation: Abatacept (Orencia) is a soluble CTLA-4 analog that prevents antigen-presenting cells (APCs) from delivering the co-stimulatory signal by binding to B7 proteins, This prevents the T cells from being fully activated, and even downregulates them. T cells are activated by two signals. The first signal is when the T cell receptor binds a specific antigen brought to it by an (APC). The second signal occurs when the T cell and APC communicate by a second set of proteins , a T cell protein called CD28 that binds to APC B7 proteins CD80/86 activating both the T cell and the APC. To turn itself off, the T cell will bring in CTLA-4 that blocks the binding of CD28 to CD80/86. Indications for use: RA, juvenile idiopathic arthritis, psoriatic arthritis Side effects: A higher risk of infections when taking this medication. ❖ Patient should be tested for tuberculosis and hepatitis b and c. ❖ Live vaccines should not be given concurrently or within 3 months of stopping this medication. Adaptive Immunity – Cytokines: interleukin 17 is a family of pro-inflammatory cytokines produced by a group of T helper cell known as T helper 17 cells in response to their stimulation with IL-23. IL-17 induces the production of many other cytokines (IL-6, IL-1β,TGF-β, TNF-α), chemokines, and prostaglandins from many cell types thus playing an important role in inflammatory and allergic reactions. IL-17 inhibitors: Secukinumab (Cosentyx), Ixekizumab (Taltz), Brodalumab (Siliq) Are monoclonal antibodies that bind either IL-17 (secukinumab, ixekizumab) or IL-17 receptor (brodalumab) preventing the subsequent inflammatory signaling. Uses: psoriasis , arthritis and ankylosing spondylitis. Adverse reactions: A higher likelihood of infections upper rtis & herpes infections. Runny nose & diarrhea. IBDs. ❖ Live vaccines should be avoided while using an IL-17 blocking therapy. Anti-IL-23 Biologics Guselkumab (Tremfya) ❖ Is a monoclonal antibody that block the functions of IL-23 cytokine. ❖ IL-23 is an inflammatory cytokine mainly secreted by activated DCs, macrophages or monocytes & B cells. ❖ It is important for keeping Th17 cells (that make IL-17) alive, also it induces proliferation of CD4 memory T cells and promotes angiogenesis. use: Psoriasis Side effects: Upper respiratory tract , fungal skin and herpes simplex infections. Headache, injection site reactions, joint pain, diarrhea & gastroenteritis. Anti-IL-12/23 Biologics: Ustekinumab (Stelara) Is a monoclonal Ab targeting IL-12 and IL-23 cytokine receptors and binds to a part of the IL- 12 and IL-23 receptors that is shared, called p40 subunit. IL-12 is a cytokine that is naturally produced by DCs, macrophages, neutrophils, and B-cells in response to antigenic stimulation. It stimulates the growth and function of T cells, the production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) from T cells and (NK) cells, and enhances the cytotoxic activity of NK cells and CD8+ cytotoxic T cells. Indications for use: Psoriasis, psoriatic arthritis, Crohn’s disease AD reactions: Higher risk of infection Allergic reactions Headache & tiredness. Anti-IL-5 Biologics: Mepolizumab, Reslizumab , Benralizumab Are monoclonal Abs that target either IL-5 cytokine (mepolizumab and reslizumab) or IL-5 receptor (benralizumab) thereby blocking immune responses. IL5 is an interleukin produced by type-2 T helper cells and mast cells that stimulates B cell growth and increases immunoglobulin secretion - primarily IgA. It is also a key mediator in eosinophil activation and it’s associated with the cause of several allergic diseases including allergic rhinitis and asthma Indications for use: Severe eosinophilic asthma, hypereosinophilic syndrome (HES), and other eosinophilic related disorders. Adverse reactions: Headache, injection site reactions & muscle spasm Increased risk of infection. ❖ If subject has a helminth infection, it should be treated before starting these medications. ❖ If subject gets a helminth infection that does not clear with treatment while on the IL-5 targeted medications, then treatment should be stopped. Anti-IL-4/IL-13 Biologics: Dupilumab (Dupixent) Is a monoclonal antibody that blocks IL-4 Receptor alpha thereby blocking IL-13 & IL-4 pathways. IL-4 & IL-13 are produced by mast cells, Th2 cells, eosinophils and basophils. IL-4 : induces the activation of B cell and T cell proliferation, and the differentiation of B cells into plasma cells. It is a key regulator in humoral and adaptive immunity, As it induces B cell class switching to IgE, and up- regulates MHC class II production. IL-13 is a central regulator in IgE synthesis, mucus hypersecretion & airway hyperresponsiveness. It is also a mediator of allergic inflammation and helps in parasitic expulsion. Indications for use: Atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps Side effects: Very small increased risk for getting skin infections, flu, or cold virus infections Allergic reactions & conjunctivitis. ❖ The recommendations are to avoid live vaccines ( varicella) but not killed or inactive vaccines when on this medication. ❖ If subject is living in an area where there are helminths, it should be monitored periodically. Biologics Targeting IgE: Omalizumab (Xolair) Is a monoclonal antibody that binds IgE – Ab in plasma, body fluids & on B cells surface. IgE is often referred to as the “allergy antibody”. When IgE binds to an allergen, it causes release of histamine and other molecules that cause an allergic response (itching, redness, hives). Indications for use: Allergic asthma, Chronic urticarial Adverse reactions: Increased risk of parasitic & helminthes infection. Anaphylaxis Increased risk of cardiovascular & cerebrovascular diseases. Lymphocyte Movement: Vedolizumab (Entyvio) Is a monoclonal antibody that binds α4β7 integrin (a protein on the outside of white blood cells that help them get to the gut) causing gut selective anti- inflammatory activity. Indications for use: Inflammatory bowel disease (ulcerative colitis and Crohn’s) Adverse effects: Rates of overall infection are slightly higher There are reports of abscesses in the lower digestive tract and bacterial infections in patients using this medication. JAK Inhibitors: Tofacitinib, Upadacitinib, Baricitinb ❖ are monoclonal antibodies that target (Janus Kinase) JAK enzymes which are tyrosine kinase proteins inside of cells that relay signals from the outside of the cell to the nucleus. Many different cytokine signals use JAKs to transmit messages in the cells. ❖ In diseases where there is too much inflammation, blocking JAKs can help to lower the amount of inflammation by decreasing the signals that tell the cell to make and release inflammatory molecules like cytokines. Indications for use: Rheumatoid arthritis, psoriatic arthritis, ulcerative colitis Adverse effects: an increased amount of infections( herpes zoster). Live vaccines should not be given concurrently. Immunity Boosters Herbs that boost immunity https://www.northwell.edu/news/in-the- news/10-herbs-that-help-boost- immunity-current-studies