The microcirculation and inflammation: Site of action for glucocorticoids

The glucocorticoid hormones and their synthetic derivatives are potent supp ressors of inflammatory and allergic pathologies. Their widespread efficacy is the result of multiple modes of action occuring predominantly at the le vel of the microcirculation. Indeed the glucocorticoids interfere with the function of all of the cellular components of the microcirculation associat ed with an inflammatory response. These agents inhibit vasodilatation of th e arteriolar and capillary beds, therefore preventing the increase in blood flow that characterizes the initial stages of the inflammatory response. T hey also prevent increases in vascular permeability in the capillary and po st-capillary venule, thereby reducing exudate formation. Finally, the gluco corticoids potently suppress leukocyte emigration across post-capillary ven ules. However, this promiscuity of the glucocorticods to act at multiple si tes also endows this class of drugs with major side effects associated with chronic treatment. We propose that one way to progress forward is to under stand better the effects of glucocorticoids within the microcirculation. Th is may aid identification of specific molecular sites of action and therefo re the development of novel glucocorticoid molecules with fewer side effect s.