Itraconazole suppresses an elicitation phase of a contact hypersensitivity reaction.
Contact dermatitis is caused by epicutaneous exposure to environmentally and/or industrially derived allergens. As the exposure is unavoidable in many instances, therapeutic suppression of allergic inflammation appears to be of clinical relevance. It was recently reported that itraconazole (ITZ), an anti-fungal agent, may be of therapeutic importance in allergic skin diseases. Therefore, we were interested in the effect of ITZ on contact hypersensitivity (CHS). Mice (C3H/HeN or Balb/c) were administered with ITZ orally before sensitization or challenged with haptens (dinitrofluorobenzene or oxazolone). Consequently, the administration of ITZ before challenge, but not before sensitization, significantly suppressed the reaction. Intriguingly, ITZ failed to suppress the irritant dermatitis induced by croton oil or benzalkonium chloride, suggesting that it may affect molecule(s) rather selectively involved in the elicitation of CHS. To further analyze mechanisms involved, splenic T cells obtained from sensitized or naive mice were stimulated with plate-bound anti-CD3 in the presence or absence of ITZ and release of cytokines was tested by ELISA. T cells from hapten-immunized mice produced a significant amount of IFN-gamma, which was markedly suppressed by ITZ. Our study demonstrates that ITZ selectively suppresses the elicitation phase of CHS possibly via downmodulation of IFN-gamma.
Ausaneya
Urupongsa
U
Department of Dermatology, Kinki University School of Medicine, 377-2 Ohnohogashi, Osakasayama-city, Osaka 589-8511, Japan.
Kawada
Akira
A
Aragane
Yoshinori
Y
D000284:Administration, Oral; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000276:immunology; D017453:Dermatitis, Irritant / Q000188:drug therapy; D004139:Dinitrofluorobenzene / Q000276:immunology; D017964:Itraconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D017252:CD3 Complex; D016207:Cytokines; D017964:Itraconazole; D004139:Dinitrofluorobenzene