High-dose proinflammatory cytokines induce apoptosis of hair bulb keratinocytes in vivo

Background Hair loss following skin inflammation may in part be mediated by keratinocyte (KC) apoptosis. While the effects of different cytokines or other apoptosis stimulating agents such as interferon (IFN)-gamma or tumour necrosis factor (TNF)-alpha on KC apoptosis in vitro have been addressed in several studies, little is known about the effects of proinflammatory cytokines on KC apoptosis in vivo. Objectives To study the effects of intradermally injected TNF-alpha, interleukin (IL)-1 beta and IFN-gamma on KC apoptosis in the back skin of C57BL/6 mice. Methods Apoptosis in epidermal and hair bulb KCs was analysed by immunohistology using TUNEL staining. Results Injection of TNF-alpha induced a significantly higher number of apoptotic cells within the epidermis than vehicle; all three proinflammatory cytokines together further increased their number. Intrafollicular hair bulb KCs were much more susceptible to apoptosis induction by TNF-alpha or IL-1 beta; their injection significantly upregulated apoptosis after 6 h, which was further increased after 24 h. The combination of all cytokines together accelerated intrafollicular apoptosis after 6 h by doubling the number of apoptotic cells per hair bulb, compared with the effects of TNF-alpha or IL-1 beta alone. Conclusions These data suggest that programmed cell death of proliferating KCs in vivo can be induced by proinflammatory cytokines.