Regulation of immune activity by mild (fever-range) whole body hyperthermia: effects on epidermal Langerhans cells

Inflammation of the skin and systemic fever, both of which occur with injur y or infection, include a hyperthermic component that many believe constitu tes a physiological stress. Such increases in local or systemic body temper ature may also have a regulatory effect on immune function. Langerhans cell s (LCs), the dendritic cells of the skin, continuously monitor the extracel lular matrix of the skin by taking up particles and microbes that they then carry to draining lymph nodes for presentation to T lymphocytes. We hypoth esize that the thermal element of inflammation and/or fever may help regula te the activation and migration of LCs out of the epidermis. To test this h ypothesis, Balb/ c mice were exposed to a mild (39.8 degreesC +/- 0.2 degre esC), long-duration (6 hours) whole body hyperthermia (WBH) treatment, whic h mimics the thermal component of fever. The number of LCs and their morpho logy were analyzed at various time points up to 7 days after the initiation of WBH. The LCs of the ear epidermis were visualized using a fluorescein i sothiocyanate-conjugated antibody specific for the major histocompatibility complex (MHC) class II molecule and confocal microscopy. Although MHC clas s II staining was diffuse on the surface of the LC body and dendritic exten sions of both WBH and control samples, the WBH-treated LCs exhibited a more punctate morphology with fewer dendritic processes compared with control L Cs. A significant decrease in the number of LCs was also observed 1 to 5 da ys after WBH treatment. Furthermore, in vitro heating of Balb/c ear skin cu ltures at 40 degreesC for 6 to 8 hours enhanced the numbers of viable LCs t hat migrated into the culture wells. These results suggest that WBH treatme nt stimulates epidermal LCs in the absence of foreign antigen.