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Glucocorticoids
  1. F Buttgereit

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People are bound to think: Oh no! Is yet another book about drugs that we are using successfully every day really necessary? Well, the answer to this question is: Yes, it is! More than 50 years after the clinical introduction of these drugs, updates are necessary to establish Milestones in drug therapy (the title of the series published by Birkhäuser). Sometimes unnoticed by all who use glucocorticoids, new, not always spectacular, but still significant knowledge has been gained about these vital drugs and how they should be administered. The authors try to put this across in a readable form, which means that known information is recapitulated concisely and new information is included. A very good example are the chapters that deal with the basic mechanisms of action. However, the only real criticism also applies at this point: some comments are redundant and tighter editing would have improved individual contributions.

Renowned authors reflect upon the most important facets of treatment with glucocorticoids. These facets include the history as well as basic biology, the development of synthetic compounds, extensive discussions about the glucocorticoid receptor, the dynamics of cytokine and other gene regulations by glucocorticoids, the interrelationship between exogenous and endogenous steroids, and a clinical section which deals with the use of steroids in asthma, arthritis, and inflammatory bowel disease. Allan Munck, one of the wise men of steroid research, describes the history of the glucocorticoids graphically and in detail. He has enriched research in this field with significant contributions since the beginning of the 1960s and now looks back amusingly and expressively on the past decades. Luca Parente's contribution ranges from naturally occurring to synthetic glucocorticoids and their effects in the organism. The sections that deal with the desired anti-inflammatory/immunomodulatory effects and adverse reactions give a valuable overview.

A few chapters should be highlighted that are of particular interest for both rheumatologists and clinical immunologists. That on molecular and cellular aspects of cytokine regulation by glucocorticoids has been prepared very carefully from a didactic point of view. It not only describes T cell activation and the effect of glucocorticoids thereon, but also provides useful information for an understanding of the function and regulation of cytokines. It is recapitulated that the central therapeutic effects of glucocorticoids are ultimately the inhibition of the synthesis of interleukin 2 and interleukin 6; glucocorticoids influence the transcription of around 1% of all genes! However, they also have an influence on the translational and post-translational mechanisms by which proteins are synthesised, processed, and exported from cells. This fact applies, in particular, to the influence on cytokine metabolism. Just to mention a few key concepts: post-transcriptional, translational, and post-translational mechanisms; modulation of cytokine receptors; indirect effects that occur as a result of the extensive interactions among various cytokines.

The chapter written by John Kirwan is worth reading for the rheumatologist, as it deals with the clinical aspect of the systemic administration of glucocorticoids in chronic inflammatory arthritis (typified by rheumatoid arthritis (RA)), in vasculitic episodes typified by those in systemic lupus erythematosus, and in polymyalgia rheumatica and temporal arteritis. It is cleverly written, because it questions apparently known facts, especially taking the example of RA. The important very short term anti-inflammatory effects are accepted and are broadly exploited. But is the risk/benefit potential also positive for medium and long term treatment? Do the glucocorticoids perhaps have a much more fundamental influence on the development and progression of RA than previously thought? Is there a differentiated and even treatment-time-dependent influence on synovitis, on the one hand, and on radiological progression, on the other? Possible answers to these exciting questions will not be anticipated here. However, this chapter, in particular, can be recommended, broadening as it does our picture of reality that is sometimes restricted to standard viewpoints.

The non-expert in the field might have wished for a little more clarity occasionally in the illustrations. The references to the individual chapters take into account publications up to and including the year 2000. Overall, this is a good example of how knowledge on established drugs such as the glucocorticoids can be clearly updated.