Anti-inflammatory effects of glucocorticoids

The most important clinical application of glucocorticoids and their semisynthetic analogs is their anti-inflammatory activity, discovered in 1949 by Hench and co-workers. The profound anti-inflammatory effects of glucocorticoids arise from the combined effects of these steroids on both the cellular and molecular mediators of inflammation these effects are separate from the metabolic effects described above and further indication of the widespread diversity of macromolecules to which steroids can bind. Glucocorticoids suppress inflammation at the cellular level by downregulating the concentration, distribution, and function of leukocytes (white blood cells) that profoundly influence inflammation and response to infection within the body (In this way, steroids help to mediate the overlap between the endocrine systems [chapter 5] and the immune systems [chapter 6]). Glucocorticoids also suppress inflammation at the molecule level by suppressing inflammatory cytokines, chemokines, and other molecular mediators of inflammation. 

Evidence also suggests that leukotriene inhibitors can be combined with other drugs (glucocorticoids, beta agonists) to provide optimal management in specific patients with asthma and COPD.11,60 In particular, it appears that these drugs may enhance the anti-inflammatory effects of glucocorticoids, and may therefore provide therapeutic effects at a relatively... 

Arachidonic acid is stored mainly in phospholipids of cell walls, from which it is mobilised largely by the action of phospholipase. Glucocorticoids prevent the formation of arachidonic acid by inducing the synthesis of an inhibitory polypeptide called lipocortin-1 the capacity to inhibit the subsequent formation of both prostaglandins and leukotrienes, explains part of the powerful anti-inflammatory effect of glucocorticoids (for other actions, see p. 664). 

Therapeutic profile GCR antagonists have potential for use in adrenocortical hyperplasia, as in Cushing s disease. Development of GCR agonists from 1,2-DQs would expand indications to those for the broad anti-inflammatory effects of glucocorticoids. 

A few patients with chronic inflammatory iilncs.scs such as asthma, rheumatoid arthritis, and lupus develop resistance to the anti-inflammatory effects of the glucocorticoids. The... 

There are essential structural features that are necessary for glucocorticoid activity. The natural glucocorticoids also interact with the mineralocorticoid receptor and, therefore, will have salt-retaining properties. A large number of synthetic analogues have been prepared to decrease the mineralocorticoid effects in favor of increasing the glucocorticoid (anti-inflammatory) effect of the steroids. In addition, many derivatives are prepared to enhance pharmacokinetic parameters, most notably the synthesis of lipophilic and hydrophilic esters. 

Cronstein B, Kimmel 8, Lenin R, Martiniuk F, Weissmann G. A mechanism for the anti-inflammatory effects of corticosteroids the glucocorticoid receptor regulates leucocyte adhesion to endothelial cells and expression of endothelial-leucocyte adhesion molecule-1 and intercellular adhesion molecule-1. Proc Natl Acad Sci U8A 1992 89 9991-9995. 

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

The glucocorticoids also have powerful anti-inflammatory effects and when first introduced were considered to be the ultimate answer to the treatment of inflammatory arthritis. Although there are increasing data that low-dose corticosteroids have disease-modifying properties,... 

The anti-inflammatory and immunosuppressive effects of glucocorticoids are largely due to the actions described above. In humans, complement activation is unaltered, but its effects are inhibited. Antibody production can be reduced by large doses of steroids, although it is unaffected by moderate doses (eg, 20 mg/d of prednisone). 

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