Immunosuppressive glucocorticoids at epithelial barriers in the regulation of anti-viral immune response

The anti-inflammatory action of adrenal-derived glucocorticoids has been recognized since several decades. This knowledge has found broad application in the clinics and today synthetic glucocorticoids are widely used in the treatment of various inflammatory diseases. However, the use of synthetic glucocorticoids in the treatment of diseases associated with viral infections of epithelial surfaces, like the lung or the intestine, is still under debate and seems not as efficient as desired. Basic research on the anti-viral immune responses and on regulatory mechanisms in the prevention of immunopathological disorders, however, has led us back again to focus on endogenous glucocorticoid synthesis. It has become established that this synthesis is not restricted to the adrenal glands alone, but that numerous tissues also produce glucocorticoids in situ. Extra-adrenal derived glucocorticoids have the capacity to locally control and maintain immune homeostasis under steady-state and inflammatory conditions. Here, we discuss the current knowledge of extra-adrenal glucocorticoid synthesis in the lung and the intestine, and its role in the regulation of anti-viral immune responses.