Influence of local treatments with capsaicin or allyl isothiocyanate in the sensitization phase of a fluorescein-isothiocyanate-induced contact sensitivity model.
BACKGROUND
In fluorescein isothiocyanate (FITC)-induced contact hypersensitivity models, dibutyl phthalate has been empirically used as a solvent ingredient. We have demonstrated that dibutyl phthalate has an adjuvant effect through the facilitation of trafficking FITC-presenting dendritic cells (DC) from the skin to draining lymph nodes. Here we investigated the effects of local pretreatment with substances that are capable of desensitizing sensory neurons in the sensitization phase.


METHODS
Local pretreatment of BALB/c mice with capsaicin (epicutaneous), allyl isothiocyanate (epicutaneous) or a truncated form of calcitonin gene-related peptide (CGRP(8-37); intradermal) was performed before contact sensitization to FITC. The ear swelling test was employed to monitor sensitization. The appearance of FITC-presenting CD11c-positive cells in the draining lymph nodes was detected by flow cytometry. Cytokine production in local lymph node cell cultures was determined by ELISA.


RESULTS
The ear swelling response was reduced in mice pretreated with capsaicin or allyl isothiocyanate. DC trafficking and maturation (based on the levels of co-stimulators CD80 and CD86) were inhibited. Interleukin-4 production by local lymph nodes was suppressed with allyl isothiocyanate but not with capsaicin. Pretreatment with CGRP(8-37) suppressed sensitization to FITC.


CONCLUSIONS
Local pretreatment with substances that are capable of desensitizing sensory neurons through the respective transient receptor potential channels suppressed skin sensitization to FITC in a mouse model. This was associated with reduced trafficking and maturation of FITC-presenting DC. A CGRP antagonist also suppressed the sensitization to FITC, suggesting the possible involvement of sensory neurons in sensitization.
Maruyama
Takashi
T
Laboratory of Microbiology and Immunology and COE Program for the 21st Century, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan.
Iizuka
Hiromi
H
Tobisawa
Yuki
Y
Shiba
Takahiro
T
Matsuda
Tomoko
T
Kurohane
Kohta
K
Imai
Yasuyuki
Y
D019264:Adoptive Transfer; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors; D002211:Capsaicin / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003877:Dermatitis, Contact / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology*; D017879:Isothiocyanates / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009475:Neurons, Afferent / Q000187:drug effects*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000187:drug effects
D016207:Cytokines; D017879:Isothiocyanates; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C004471:allyl isothiocyanate; D016650:Fluorescein-5-isothiocyanate; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin