Anti immunosuppressive

Tao, S. and P. E. Lipsky. 2000. The Chinese anti-immunosuppressive herbal remedy Tripterygium wilfordii Hook F. Complement. Altem. Ther. Rheum. Dis. II 26(1) 29-50. 

Traditionally, Garcinia species have been used as anti-inflammatory, anti-immunosuppressive, antiprotozoal and antimicrobial agents. The various medicinal properties attributed to Garcinia are ... 

Inhibition of immunomodulatory cytokines (Fig. 1) Anti-T-cell receptor antibodies Muromonab (OKT3, Orthoclone ) binds to the CD3 complex of the T-cell receptor and induces depletion of T-lymphocytes. It is applied to prevent acute rejection of kidney, liver, and heart allografts. Rapid side effects (within 30-60 min) include a cytokine release syndrome with fever, flu-like symptoms, and shock. Late side effects include an increased risk of viral and bacterial infections and an increased incidence of lymphproliferative diseases due to immunosuppression. 

Humanized recombinant anti-IL-2 receptor antibodies (Basiliximab, Simulect , and Daclizumab Zenapax ). These antibodies bind with high affinity to the IL-2 receptor on T-lymphocytes and prevent activation and clonal expansion of anti-allograft T-lymphocytes by endogenous IL-2. They are used to prevent kidney allograft rejection. The main side effect is immunosuppression. 

Corticotropin is used for diagnostic testing of adrenocortical function. This drug may also be used for the management of acute exacerbations of multiple sclerosis, nonsuppurative thyroiditis, and hypercalcemia associated with cancer. It is also used as an anti-inflammatory and immunosuppressant drug when conventional glucocorticoid therapy lias not been effective (see Display 50-1). 

The ghicocorticoids are used as replacement therapy for adrenocortical insufficiency, to treat allergic reactions, collagen diseases (eg, systemic lupus erythematosus), dermatologic conditions, rheumatic disorders, shock, and other conditions (see Display 50-1). The anti-inflammatory activity of these hormones make them valuable as anti-inflammatories and as immunosuppressants to suppress inflammation and modify the immune response... 

The goals of maintenance immunosuppression are to further aid in preventing acute rejection episodes and to optimize patient and graft survival Anti-rejection medications require careful selection and dosage titration to balance the risks of rejection with the risks of adverse events. Common maintenance immunosuppressive agents can be divided into four basic medication classes ... 

Treatment for PTLD is still controversial however, the most common treatment options include reduction of immunosuppression, chemotherapy,11,82 and anti-B cell monoclonal antibodies.79... 

Recently, the notion that the chronicity of inflammation may not actually drive the fibrogenic process has been widely appreciated (Tables 1, 2, and 3). Some propose that it is indeed the alteration of the mesenchymal cell phenotypes that disrupts the balance between collagen synthesis and degradation in the wound-healing process, highlighted by clinical evidence that shows unsuccessful treatment of fibrosis with anti-inflammatory or immunosuppressive drugs (18,19). One scenario is that mesenchymal cells (myofibroblasts and fibroblasts) are phenotypically altered and thus do not undergo apoptosis after resolution. 

In China, the plant is used to treat rheumatic inflammation. The anti-inflammatory property is substantiated, and a surprising amount of evidence is available. Note that the main anti-inflammatory principle of Tripterygium uiildfordii is a diterpene triepoxide known as triptolide, which posseses potent anti-inflammatory and immunosuppressive properties (103,104). 

Zheng J. Screening of active anti-inflammatory, immunosuppressive and anti-fertility components of Tripterygium wildfordii III. A comparison of the anti-inflammatory and immunosuppressive activities of 7 diterpene lactones epoxides compounds in vivo. Zhongguo Yixue Kexueyuan Xuebao 1991 13 391-397. 

Corticosteroids (e.g., beclomethazone, flunisolide, triamcinolone) have anti-inflammatory and immunosuppressant actions. These drugs are used prophylactically to prevent the occurrence of asthma in patients with frequent attacks. Because they are not useful during an acute attack, corticosteroids are prescribed along with maintenance bronchodilators. These drugs are also administered by inhalation. Cromolyn is another anti-inflammatory agent used prophylactically to prevent an asthmatic attack. The exact mechanism of action of cromolyn is not fully understood however, it is likely to involve the stabilization of mast cells. This prevents the release of the inflammatory mast cell mediators involved in inducing an asthmatic attack. Cromolyn has proven effective in patients with exercise-induced asthma. 

The answer is c. (Katzung, pp 608-609, 932-9.13.) Methotrexate is classified as an anti metabolite with therapeutic uses in cancer chemotherapy and as an immunosuppressive agent indicated in the treatment of severe active classical rheumatoid arthritis. Leucovorin is related to methotrexate in that it is an antagonist of its actions. It can supply a source of reduced folate for the methylation reactions that are prevented by methotrexate. 

Of the following mechanisms of anti-inflammatory and immunosuppressive effects of glucocorticoids, which one is uniformly observed ... 

Misoprostol C22H38Os 382.5 immunosuppressive agent Anti-ulcer agent... 

Most cytokines act upon, or are produced by, leukocytes (white blood cells), which constitute the immune and inflammatory systems (Box 8.1). They thus play a central role in regulating both immune and inflammatory function and in related processes such as haematopoiesis (the production of blood cells from haematopoietic stem cells in the adult bone marrow), as well as in wound healing. Indeed, several immunosuppressive and anti-inflammatory drugs are now known to induce their biological effects by regulating production of several cytokines. 

The major types of drug therapy used in IBD include aminosalicylates, glucocorticoids, immunosuppressive agents (azathioprine, mercaptopu-rine, cyclosporine, and methotrexate), antimicrobials (metronidazole and ciprofloxacin), and agents to inhibit tumor necrosis factor-a (TNF-a) (anti-TNF-a antibodies). 

The anticonvulsant phenytoin, and to a lesser degree carbamazepine, can inhibit the synthesis of antibodies, and in some cases these drugs can result in lymphoproliferation [77-79]. These effects on the immune system could be viewed as a type of autoimmunity. The relationship between such effects and autoimmunity are still not clear, although the more recent observations that cytokines and anti-cytokines can cause autoimmunity support the existence of such a relationship. The previous edition of this book contained an extensive discussion of the possible relationship between immunosuppression and autoimmunity [80], Phenytoin and carbamazepine can also cause a lupus-like syndrome although the incidence is lower than with many other drugs. 

Corticosteroids synthesized by the adrenal gland are mineralocorticoids and GC. Min-eralocorticoids regulate fluid and electrolyte balance by affecting ion transport in the kidney. Cortisol, the primary circulating GC in most species (including humans), has many activities, including resistance to stress, regulation of intermediary metabolism, and immunosuppressive and anti-inflammatory effects. GC synthesis and secretion is... 

De Bosscher, K., Vanden Berghe, W., and Haegeman G., Mechanisms of anti-inflammatory action and of immunosuppression by glucocorticoids Negative interference of activated glucocorticoid receptor with transcription factors, J. Neuroimmunol., 109, 16, 2000. 

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