Influence of dibutyl phthalate on dermal sensitization to fluorescein isothiocyanate.
What limited evidence there is indicates that the formulation in which a chemical allergen is encountered on the skin can have a marked impact upon the induction of cutaneous immune responses and the subsequent development of contact sensitization. The purpose of the present investigations was to examine further this phenomenon by analysis of the influence of dibutyl phthalate (DBP) on dermal sensitization to fluorescein isothiocyanate (FITC), a skin sensitizing fluorochrome. Addition of DBP augmented very substantially, in a dose-dependent fashion, the ability of topically applied FITC to stimulate proliferative responses in mice by draining lymph node cells (LNC), a correlate of skin sensitizing potential. Under these conditions, exposure of mice to DBP alone failed to elicit significant LNC responses. The influence of DBP on the accumulation of dendritic cells (DC) induced by FITC was examined also. Although 10% DBP had little effect on the numbers of DC found within draining nodes 18 hr following exposure of mice to FITC, the phthalate did result in a very substantial increase in the frequency of lymph node DC bearing detectable antigen (FITC+ DC). Furthermore, in the presence of DBP the median amount of FITC associated with antigen-bearing DC was higher. In vitro skin absorption studies indicated that DBP was associated with a small increase in percutaneous absorption of FITC. Collectively these data demonstrate that the vehicle formulation can exert a marked influence on dermal sensitization and that one mechanism which may be relevant is the increased acquisition of antigen by DC, associated possibly with altered penetration of the allergen into or through the skin.
Dearman
R J
RJ
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, United Kingdom.
Cumberbatch
M
M
Hilton
J
J
Clowes
H M
HM
Fielding
I
I
Heylings
J R
JR
Kimber
I
I
D000287:Administration, Topical; D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D003993:Dibutyl Phthalate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D012869:Skin Absorption / Q000187:drug effects
D003993:Dibutyl Phthalate; D016650:Fluorescein-5-isothiocyanate