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.


OBJECTIVE
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.
Rückert
R
R
Institute of Immunology, Benjamin Franklin Medical Center, Free University Berlin, Berlin, Germany.
Lindner
G
G
Bulfone-Paus
S
S
Paus
R
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology*; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma