In the last decade, several new aspects of glucocorticoid (GC)-actions on immune cells have been documented. This recognition is largely obtained through clinical observations of stress-induced exacerbations of certain dermatological diseases.  In murine model systems, we demonstrated that long term-application of topical GC and its withdrawal augmented classical contact sensitivity reaction, croton oil induced-irritant reaction and IgE mediated-biphasic cutaneous reaction.     

In addition, same regimen enhanced scratching behavior in hapten-challenged mice accompanied by induction of preprotachykinin and iNOS mRNA expression in the challenged skin through activation of IL3.  These results indicate that disruption of GC metabolism in the skin by inappropriate application of GC may exacerbates cutaneous immune response.  In in vitro experiment, low dose, stress-induced level of GC significantly upregulated hapten-induced proinflammatory cytokines (IL1 α) and induced substance P peptide production from cultured  keratinocytes. Taken together our results suggest that GC plays an important role in the the homeostatic regulation of cutaneous immune system through aberrant production of tachykinin such as substance P or other epidermal cell derived cytokines.