Lactoferrin: influences on Langerhans cells, epidermal cytokines, and cutaneous inflammation.
It has been suggested previously that, in addition to other biological roles, lactoferrin (LF) may display antiinflammatory properties secondary to the regulation of cytokine expression. To explore this concept further, we have here examined in human volunteers the influence of recombinant homologous LF on the migration of epidermal Langerhans cells (LC), a process that is known to be dependent upon the local availability of certain proinflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta). In common with previous studies in mice, it was found that topical administration of LF prior to exposure at the same site to the contact sensitizer diphenylcyclopropenone resulted in a significant reduction of allergen-induced LC migration from the epidermis (measured as a function of the frequency of CD1a+ or HLA-DR+ LC found in epidermal sheets prepared from punch biopsies of the treated skin sites). However, under the same conditions of exposure, LF was unable to influence migration of LC induced by the intradermal administration of TNF-alpha data consistent with the hypothesis that one action of LF in the skin is to regulate the local production of this cytokine. Further support for this hypothesis was derived from experiments conducted with IL-1beta. This cytokine is also able to induce the mobilization of LC following intradermal injection, although in this case, migration is known to be dependent upon the de novo production of TNF-alpha. We observed that prior exposure to LF resulted in a substantial inhibition of IL-1beta-induced LC migration, data again consistent with the regulation of TNF-alpha production by LF. Collectively, these results support the view that LF is able to influence cutaneous immune and inflammatory processes secondary to regulation of the production of TNF-alpha and possibly other cytokines.
Kimber
I
I
Syngenta Central Toxicology Laboratory, Macclesfield, Cheshire, UK. ian.kimber@syngenta.com
Cumberbatch
M
M
Dearman
R J
RJ
Headon
D R
DR
Bhushan
M
M
Griffiths
C E M
CE
D000287:Administration, Topical; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000276:immunology*; D004817:Epidermis / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007781:Lactoferrin