Neuroimmune communication in skin: Far from peripheral

The precise nature of the link between stress and exacerbation of skin inflammation has puzzled researchers and clinicians alike. The traditional explanation is that immune balance is altered by activation of two stress axes: activation of the hypothalamic-pituitary-adrenal (HPA) axis raises cortisol levels, and activation of the sympathetic nervous systems raises adrenaline levels ( Figure 1). In this issue, Pavlovic et al. (2008) provide evidence for a third stress axis and report that stress travels to the skin through peripheral neuropeptidergic nerve fibers and exacerbates the neurogenic inflammatory aspect of cutaneous dermatitis. Clarification of the role of this alternative stress axis may enable the design of novel therapeutic strategies.