oa Edtorial [Hot topic: Glucocorticoids from Chemistry to Clinics (Executive Editor: Fortunato Vesce)]

The rationale for promoting a multidisciplinary update on glucocorticoids can be identified from one side in the growing evidence of the role of inflammation in the pathogenic mechanism of many diseases, and from the other in the physiologic control upon the regulators of tissue functions that, in addition to their anti-inflammatory action, these hormones exert. When we think of inflammation our mind goes back to the five historical signs: rubor, calor, dolor, tumor and functio laesa: however it appears today that those signs represent late features of the pathologic process, while the role of their mediators is subverted much earlier in the development of different diseases. Indeed, it is known that such mediators, before being responsible for inflammatory changes, regulate important functions, among which cell social behavior, angiogenesis, haemostasis, smooth muscle contraction, and many others upon which our physiologic wellbeing depends. As to such subtle progressive subversions, it appears of key interest today that certain critical genes polymorphisms may be responsible for some harmful inflammatory responses. For instance, they are reported to increase the risk of preterm birth and of related maternal-foetal diseases, while the incidence of such complications is decreased by those polymorphisms addressing the maternal immune response against inflammation [1]. The association with gene polymorphisms has also been reported to increase the risk of developing asthma and chronic obstructive pulmonary disease, and their role is considered crucial for the development of new strategies for lung disease management [2-4]. Indeed, these observations suggest that high risk populations could benefit from compounds such as glucocorticoids, able to rebalance the inflammatory response mediators towards physiologic homeostasis. However, differing from other hormones widely introduced in medical practice, the use of glucocorticoids is generally restricted to treating advanced pathologic conditions. Furthermore, one relevant matter is that, in the majority of the situations for which they are used, essaying the circulating glucocorticoid concentration is devoid of therapeutic information, and therefore it is of no help in the management of the disease. This suggests that the main features of hormonal involvement in pathologic processes may occur at a tissue level, and therefore that at such level they should be searched for. For instance, some cases of recurrent abortion are characterized by an increased number of decidual natural killer cells (NK), with no other clinical evidence than pregnancy loss. These cases have been shown to benefit from glucocorticoid treatment, bringing NK concentration back to normal values, and favoring a positive outcome of gestation [5,6]. These observations suggest that the clinical use of glucocorticoids can be approached looking at them as natural regulators of functions, rather than dangerous drugs to be avoided. Such point of view reflects the opinion that early changes in the balance of the mediators of cellular functions represent the cause of a pathology gradually evolving towards inflammation, rather than its mere consequence.