Immunosuppressive action

Propylthiouracil (PTU), but not methyl-mercaptoi-midazole (MMI), has an additional peripheral effect. It inhibits the monodeiodination of thyroxine to triiodothyronine by blocking the enzyme 5 mono-deiodinase [1]. In humans the potency of MMI is at least 10 times higher than that of PTU, whereas in rats PTU is more potent than MMI. The higher potency of MMI in humans is probably due to differences in uptake into the thyroid gland and subsequent metabolism, because in vitro inhibition of thyroid peroxidase by MMI is not significantly more potent than by PTU [1, 6]. Whether antithyroid drags have additional immunosuppressive actions is a matter of discussion [1, 2]. 

During the maintenance phase dose reductions are aimed. However, in most cases a dual or triple combination therapy is still necessary. The use of drugs with different mechanisms of immunosuppressive action allows the application of lower doses additionally resulting in decreased toxicity. 

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. 

Prednisolone also exhibits anti-shock, anti-allergy, anti-inflammatory, and immunosuppressive action. It raises glucose levels in the blood, increases potassium secretion, and reduces sodium secretion from the organism. 

Kiessig et al. studied the interaction of the immunosuppressant drug cyclosporin A and some derivatives to its cellular receptor protein cyclo-philin (26). The cyclophilin-cyclosporin A complex mediates the immunosuppressive action of cyclosporin A by inhibition of the phosphatase calci-neurin. Using ACE in the equilirium-mixture mode, a separation of the cyclophilin-cyclosporin A complex and the unbound cyclophilin was achieved. The approach allowed a qualitative estimation of the binding affinity of cyclosporin A derivatives compared to cyclosporin A. For the calculation of binding constants, electrophoretically mediated microanalysis was applied. 

Another drug whose immunosuppressive action is mediated by the complexation with a cellular protein of the immunophilins is FK506. FK506 binds to proteins of the FKBP family. The complex formed is involved in the inhibition of the phosphatase calcineurin, similar to the mode of action of CsA after binding to cyclophilin. The ACE method was used to detect... 

Rapamycin (sirolimus), a macrolide antibiotic, has been used recently in organ transplantation for its potent immunosuppressive actions by inhibiting both cytokine mediated and growth factor mediated proliferation of smooth muscle cells and lymphocytes [55, 56]. In the RAVEL trial of non-acute single vessel lesions, the Sirolimus-eluting stent was compared to bare metal stent (BMS) in a 1 1 fashion [57]. One-year major adverse cardiovascular events and 6 month neointimal proliferation as assessed by late luminal loss (-0.01 0.33 mm in Sirolimus stent versus 0.80 0.53 mm in BMS) were improved. The Sirolimus-eluting stent thus virtually eliminated in-stent restenosis with no evidence of edge effect, dissection, or in-stent thrombosis. 

Azathioprine is a relatively powerful antiinflammatory agent. Although its beneficial effect in various conditions is principally attributable to its direct immunosuppressive action, the antiinflammatory properties of the drug play an important role in its overall therapeutic effectiveness. 

DNA s5mthesis and also interfere with cell replication. Alkylating agents has got cytotoxic action and damage the nuclei of growing and multiplying cells. They have got immunosuppressant action also and suppress antibody production. They also have radiomimetic (like ionizing radiation) actions. 

Bierer, B. E., Somers, P. K., Wandless, T. J., Burakoff, S. J., and Schreiber, S. L. (1990b). Probing immunosuppressant action with a nonnatural immunophilin ligand. Science 250, 556-559. 

In conclusion, the in vivo activity of available delta opioids is complex. DPDPE, or even Delt, administered ICV seems to recruit mu receptors and, from all the data, it appears that delta agonists often have mixed mu/ delta activities. More selective delta agonists need to be produced to explore delta receptor pharmacology. The examination of nonanalgesic activities of delta ligands in opioid receptor knockout mice has been very informative while the convulsive effect of SNC 80 seems indeed delta receptor mediated, the addictive activity of Delt most probably results from mu receptor activation and the immunosuppressive action of NTI is mediated by a nonopioid mechanism. 

Sirolimus (rapamycin) is another macrolide, produced by Streptomyces hydroscopi-cus. Its immunosuppressant action, evidently, does not appear to involve inhibition of calcineurin. It forms a complex with the FK protein, imparting a special conformation on it and the complex then inhibits the mTOR (mammalian target of rapamycin) phosphatase. The latter operates in the signaling path leading from the interleukin-2 receptor to activation of mitosis in lymphocytes. Thus, sirolimus inhibits lymphocyte proliferation. It is approved for the prevention of transplant rejection. 

Drying lotions should not be used on skin lesions because they may increase scarring. In the child or adult for whom the skin lesions itch or are irritating, an oral antihistamine may help to prevent scratching, which can lead to secondary infection and thereby scarring. Recommended agents include oral chlorpheniramine or diphenhydramine.The use of cimetidine is controversial as an H2 blocker, oral cimetidine has an immunosuppressive action. The effects are not always consistent, however, and use of cimetidine is risky in autoimmune disorders and organ transplant patients. 

Acorus calamus has in vitro antiprohferative and immunosuppressive actions (1). 

The molecular targets of rapamycin inhibitors (mTOR), siroiimus and everoiimus, have a distinct mechanism of immunosuppressive action different from the calcineurin inhibitors cyclosporine and TAC. As such, they are expected to be minimally nephrotoxic per se. 

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