Exogenous topical lactoferrin inhibits allergen-induced Langerhans cell migration and cutaneous inflammation in humans.
BACKGROUND
Lactoferrin (LF), an iron-binding protein found in exocrine secretions, is known to possess antibacterial properties. It has recently been proposed that LF may also influence inflammatory reactions.


OBJECTIVE
To characterize in humans the ability of recombinant homologous LF to inhibit the induced migration of epidermal Langerhans cells (LCs) from the skin, a process known to be dependent upon the proinflammatory cytokines tumour necrosis factor (TNF)-alpha and interleukin 1beta and to influence cutaneous inflammatory reactions.


METHODS
We investigated the anti-inflammatory properties of LF in human volunteers.


RESULTS
Topical exposure to LF 2 h prior to sensitization caused a significant reduction in contact allergen (diphenylcyclopropenone, DPC)-induced LC migration from the epidermis as judged by the altered frequency of cells expressing either HLA-DR or CD1a determinants. That this reduction was secondary to an inhibition of TNF-alpha production was indicated by the fact that LF failed to influence LC migration induced by intradermal injection of this cytokine. In approximately 50% of those volunteers who displayed local inflammation in response to DPC, LF was found to cause a discernible reduction in the clinical severity of the reaction, associated with reduced infiltration of inflammatory cells.


CONCLUSIONS
These data demonstrate that LF is able to influence cutaneous immune and inflammatory responses, possibly because of an impaired production of local proinflammatory cytokines.
Griffiths
C E
CE
Dermatology Centre, University of Manchester, and Department of Pathology, Hope Hospital, Salford, Manchester M6 8HD, UK. cgriffiths@fs1.ho.man.ac.uk
Cumberbatch
M
M
Tucker
S C
SC
Dearman
R J
RJ
Andrew
S
S
Headon
D R
DR
Kimber
I
I
D000328:Adult; D000485:Allergens / Q000276:immunology*; D018949:Antigens, CD1 / Q000032:analysis; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003521:Cyclopropanes / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000517:prevention & control*; D004817:Epidermis / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007781:Lactoferrin / Q000627:therapeutic use*; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012709:Serum Albumin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000485:Allergens; D018949:Antigens, CD1; D003521:Cyclopropanes; D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D007781:Lactoferrin; C029402:diphenylcyclopropenone