Immunosuppressant pathways

There is an increasing appreciation of the unifying role that the immunosuppressive pathway of... 

Immunosuppressive Pathways Through Formation of PPIase Ligand Complexes... 

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... 

Mycophenolate mofetil was approved by the FDA in 1995, and enteric-coated mycophenolic acid was approved in 2004. Both agents are considered to be adjunctive immunosuppressants. Mycophenolic acid acts by inhibiting inosine monophosphate deydrogenase, a vital enzyme in the de novo pathway of purine synthesis. Inhibition of this enzyme prevents the proliferation of most cells that are dependent on the de novo pathway for purine synthesis, including T cells.7,11,26-28... 

Recently, it has been shown that inhalation of MWNTs caused suppression of the systemic immunity without resulting in significant lung inflammation or tissue damage [82,83]. Inhaled MWNTs in fact modified the functionality of spleen cells in exposed mice [82]. Notably, the activity of cyclooxygenase (COX) enzymes in spleen was affected as a response to a cytokine (TGF(5) released from the lungs. This cytokine activated the COX pathway in the spleen, triggering T-cell dysfunction and systemic immunosuppression [83]. 

JP-8-induced systemic immunosuppression is explained in part by modulation of cytokine and inflammatory pathways. Within 48 hours of a single dermal application of JP-8 (300 pL), serum IL-10 levels increase significantly to nearly 3000 pg/mL [36], As IL-10 is known to suppress DTH responses [64,65], it is likely that modulation of this cytokine contributes to JP-8 s immunotoxicity. Furthermore, splenic T-cell proliferative responses are significantly decreased in JP-8 exposed mice, yet this effect is reversed following neutralization of IL-10, administration of IL-12, or inhibition of prostaglandin E2 (PGE2) production [60], Additional studies demonstrated suppression... 

Fig. 1. Organ/cellular pathways in the induction of CD8+ suppressor cells by the injection of antigen into the anterior chamber (AC). he injection of antigen into the AC induces a recruitment of F4/80+ monocytic cells to the iris. Interactions with iris monocytic cells, antigen and GF-p in aqueous humor induces an immunosuppressive phenotype in the recruited cells. hese cells then recirculate from the AC to the thymus and the spleen. In the spleen, F4/80+ cells interact with B cells, peripheral NK cells, recent thymic NK emigrants and CD8+ cells with the generation of CD8+ suppressor cells that effect the suppression of a D FI reaction.

Everolimus (40 Afinitor Novartis, 2009), a rapamycin analog, is the 42-0-(2-hydroxyethyl) derivative of sirolimus (34), and is marketed as an immunosuppressant by Novartis under the tradename Afinitor for use in advanced renal cell carcinoma.In March 2009, the FDA approved everolimus (40) for use against advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib. The drug works similarly to sirolimus as an inhibitor of mTOR (mammalian target of rapamycin), a serine-threonine kinase, downstream of the PI3K/AKT pathway. Everolimus (40) binds to an intracellular protein, EKBP-12, resulting in an inhibitory... 

Mycophenolate sodium (62 Myfortic Norvatis, 2003) is an immunosuppressant drug used to prevent rejection in organ transplantation. It is a selective, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novo pathway of guanosine nucleotide synthesis. Thus, mycophenolic acid (61), originally... 

Patterson, R.M. and Germolec, D.R. (1076) Gene expression alterationsin immune system pathways following exposure to immunosuppressive chemicals. Annals qfthe New York Academy of Sciences, 2006, 718-727. 

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