IL-1beta-induced Langerhans' cell migration and TNF-alpha production in human skin: regulation by lactoferrin.
In mice, the roles of cytokines in the initiation of epidermal Langerhans' cell (LC) migration are well documented; however, the mechanism of this response in humans is less well defined. The purpose of the present investigation was to examine the contribution of interleukin (IL)-1beta to human epidermal LC migration and to define further the mechanisms of this response. We demonstrate here that homologous recombinant IL-1beta administered intradermally to healthy human volunteers provides a stimulus for LC migration, with significant (P < 0.01) reductions in LC densities being observed at both 2 h and 4 h following treatment. At the later time-point of 4 h, injection of IL-1beta was also accompanied by activation of those LC remaining in the epidermis. Analysis of fluid aspirated from suction blisters formed at injection sites revealed significant (P < 0.01) tumour necrosis factor (TNF)-alpha production (2.99 +/- 1.18 pg TNF-alpha/mg protein; mean +/- s.d. of n = 10) in response to IL-1beta treatment compared with saline control injections (0.90 +/- 1.05 pg TNF-alpha/mg protein). Prior topical application of human recombinant lactoferrin (LF), an iron-binding protein found in exocrine secretions and skin, inhibited IL-1beta-mediated LC migration and also compromised the production of TNF-alpha protein as measured in suction blister fluids derived from each of the treatment sites. Taken together, these data demonstrate that IL-1beta is associated with both the stimulation of human epidermal LC migration and local TNF-alpha production. Topical treatment with LF compromises both these responses. These data suggest that topical LF may potentially represent a novel therapeutic in the treatment of skin inflammation where TNF-alpha is an important mediator.
Cumberbatch
M
M
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK. marie.cumberbatch@syngenta.com
Bhushan
M
M
Dearman
R J
RJ
Kimber
I
I
Griffiths
C E M
CE
D000328:Adult; D000704:Analysis of Variance; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D046508:Culture Techniques; D004817:Epidermis; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007271:Injections, Intradermal; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000494:pharmacology; D007781:Lactoferrin / Q000494:pharmacology*; D007801:Langerhans Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009824:Ointments; D011312:Pressure; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D009824:Ointments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007781:Lactoferrin