Immunosuppression mechanism

Sacks, D. and Anderson, C., Re-examination of the immunosuppressive mechanisms mediating non-cure of Leishmania infection in mice, Immunol. Rev. 201, 225, 2004. 

TGNs have a half-life of approximately one week with large variability (91,92). Several cytotoxic and immunosuppressant mechanisms of thiopurine action have been described (95, 96, 97, 98, 99,100). However, the major underlying mode of action in... 

Rapamycin (sirolimus) is another macrolide antibiotic that possesses potent immunosuppressant activity. Rapamycin has a chemical structure partially similar to that of tacrolimus (Fig. 2). It was first isolated from Streptomyces hygro-scopicus strains found in soil obtained on Rapa Nui (Easter Island), hence the name rapamycin [19, 20]. This compound was initially investigated as an antifungal agent and later found to have immunosuppressive activity [21]. Rapamycin also binds to FKBP, but its immunosuppressive mechanisms are distinct from those of tacrolimus and cyclosporin in that it does not act via the calcineurin pathway [22, 23]. The immunosuppressive effects of rapamycin result from its inhibition of T-cell [23, 24] and B-cell [25] proliferation. The key effect on those cells results from the blocking of the signals of several cytokines (IL-2 and IL-4), leading to interruption of the cell cycle from the G, to the S phase. Unlike tacrolimus, the complex of rapamycin and FKBP-12 does not inhibit the dephosphorylase... 

Fig. 1. The immunosuppressive mechanism of tacrolimus. (Reprinted with permission from Amaya, T., Hiroi, J., and Lawrence, I., Folia Pharmacologica Japonica 117[5], Fig. 2, p. 353.)...

Miller and Rich assumed that cyclosporin Aand itsMeBmt analogs share a common bioactive conformation. Their molecular mechanics calculations found such a conformation. The Boltzmann population of the proposed bioactive conformation correlates with the immunosuppressive activities of the compounds. 

Immunosuppression induced by sirolimus (36) appears to be mediated by a mechanism distincdy different from that of either cyclosporin or FK-506. Sirolimus markedly suppresses IL-2 or IL-4-driven T-ceU proliferation. The preclinical studies suggest that sirolimus is a potent immunosuppressive agent in transplantation and autoimmune disease models. The clinical potential of this agent depends on its toxicity profile (80). 

Type II, III, and IV allergic reactions are variants of physiologic defense mechanisms only relevant in special situations, which follow a common pathologic pattern. In general, treatment of these forms require antiinflammatory ( inflammation) or immunosuppressive strategies ( immunosuppression). Therefore, only therapy of Type I reactions will be described here. 

Immunosuppressive drugs comprise a large spectrum of substances with different mechanisms of action where T-lymphocytes represent a major target [1, 2]. In general, immunosuppressants can be divided into those that... 

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. 

The introduction of PP2B (calcinemin) inhibitors revolutionized kidney transplantation. Cyclosporine A and tacrolimus (FK506) are the principal immunosuppressants prescribed for adult and pediatric renal transplantation. Cyclosporine A was in use clinically long before its mechanism of action was elucidated. 

Q Risk for Infection related to inadequate defense mechanisms (immunosuppression)... 

Additionally, mechanisms of immunosuppression by organotins have also focused on the role of apoptosis versus proliferation arrest. The apoptotic pathway followed by organotin compormds such as dibutyltin dichloride and tributyltin chloride at high doses is... 

A patient s resistance is cmcial in determining the outcome of a medicament-borne infection. Hospital patients are more exposed and susceptible to infection than those treated in the general community. Neonates, the elderly, diabetics and patients traumatized by surgeiy or accident m have impaired defence mechanisms. People suffering fiom leukaemia and those treated with immunosuppressants are most vulnerable to infection there is a strong case for providing all medicines in a sterile form for these patients. 

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