Glucocorticoids, selective inhibition

Lee SW, Tsou AP, Chan H, et al. Glucocorticoids selectively inhibit the transcription of the interleukin ip gene and decrease the stability of interleukin ip mRNA. Immunology 1988 85 1204-1208. 

Mechanism of Action. Cyclosporine and tacrolimus (see below) are known as calcineurin inhibitors because they inhibit a specific protein (calcineurin) in lymphoid tissues. This inhibition ultimately suppresses the production of IL-2, a cytokine that plays a critical role in immune response by promoting the growth and proliferation of activated T lymphocytes and other immune cells, such as NK. cells (see Fig. 37—1).5,52 Thus, cyclosporine is one of the premier immunosuppressants because of its relative selectivity for T cells and its inhibition of a key mediator of the immune response (IL-2).41 This relatively specific inhibition is often advantageous when compared with other nonse-lective drugs such as azathioprine, cyclophosphamide, and glucocorticoids that inhibit virtually all the cells and chemical mediators involved in the immune response. 

Bhattacharyya S, Brown DE, Brewer JA, Vogt SK, Muglia LJ. Macrophage glucocorticoid receptors regulate Toll-like receptor-4-mediated inflammatory responses by selective inhibition of p38 MAP kinase. Blood 2007, 109, 4313M319. 

Mycophenolate mofetil, the morphohnoethyl ester of mycophenolic acid (rINN), is an antimetabohte that interferes with the synthesis of nucleic acids and selectively inhibits the proliferation of T and B lymphocytes. It has been used to treat psoriasis and to prevent acute renal allograft rejection in combination with ciclosporin and glucocorticoids. 

Ihara, H. and Nakanishi, S. (1990). Selective inhibition of expression of the substance P receptor mRNA in pancreatic acinar AR42J cells by glucocorticoids. J. Biol. Chem. 265, 22441-22445. 

The selectivity of hydrocortisone for the glucocorticoid receptor is not due to a different binding affinity of hydrocortisone to the two receptors but to the protection of the mineralocorticoid receptor by locally high concentrations of the enzyme 11 J-hydroxysteroid dehydrogenase, which converts cortisol (hydrocortisone) to the inactive cortisone. This enzyme is inhibited by one of the components of liquorice, and can occasionally harbour a genetic defect. Therefore both acquired (in liquorice addicts) and inherited syndromes of pseudohyperaldo-steronism can occasionally occur. 

Nimesulide is a sulfonanilide compound available in Europe that demonstrates COX-2 selectivity similar to celecoxib in whole blood assays. Additional effects include inhibition of neutrophil activation, decrease in cytokine production, decrease in degradative enzyme production, and possibly activation of glucocorticoid receptors. Its structure is ... 

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