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

Br J Dermatol. 2000 Nov;143(5):1036-9. doi: 10.1046/j.1365-2133.2000.03784.x.

Abstract

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)-1beta 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-1beta; 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-1beta alone.

Conclusions: These data suggest that programmed cell death of proliferating KCs in vivo can be induced by proinflammatory cytokines.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cytokines / pharmacology*
  • Hair Follicle / cytology
  • Hair Follicle / drug effects*
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Keratinocytes / cytology
  • Keratinocytes / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Cytokines
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma