P36 SONIC STRESS OR SUBSTANCE P INJECTION UPREGULATE INTRAFOLLICULAR APOPTOSIS, AND DOWNREGULATE FOLLICULAR PROLIFERATION IN MICE

¹Handjiski B., ²Paus R., ¹Hagen E., ¹Pliet R., ¹Joachim R., ¹Klapp B. ¹Arck P.; ¹Dept of Internal Medicine, Charité, Humboldt-Univ Berlin; ²Dept. of Dermatology, UKE, Univ of Hamburg, Germany

Stress induces specific neuroimmunological changes in murine skin, such as increased degranulation activity of mast cells and perifollicular clustering of MHC class II+ macrophages, which may represent interactions of the cutaneous nervous system with the skin immune system that have an impact on hair growth (Arck et al., JID 114:873a, 2000). In the present study, we investigated whether stress results in any growth-related, intrafollicular changes, and examined the role of a key, stress-associated neuropeptide, substance P (SP), in the modulation of intrafollicular apoptosis and proliferation, as a possible molecular link between stress and hair loss. Using a well-established murine stress model, mice with all back skin hair follicles (HF) in telogen were exposed to sonic stress. Apoptotic cells were detected by the TUNEL technique, proliferating cells by Ki67 expression. 10-20% of all telogen HF presented TUNEL+ cells in non-stressed control mice. Exposure to sonic stress significantly upregulated intrafollicular apoptosis (60% TUNEL+ HF, p <0.05). This corresponded well to a concomittant down-regulation of intrafollicular keratinocyte proliferation. Interestingly, i.c. injection of 100 nMol SP also resulted in a significantly higher percentage of TUNEL+ HF (48%) in non-stressed mice. The number of gd T cells in the infundibulum was also significantly reduced after stress or SP injection. This provides the first direct evidence that stress can alter hair growth in vivo, and invites the hypothesis that stress can induce a (SP-mediated?) macrophage attack on the HF, which inhibits HF growth via the release of macrophage cytokines (e.g. TNF-a or IL-1).