Establishment of murine model of allergic photocontact dermatitis to ketoprofen and characterization of pathogenic T cells.
BACKGROUND
Ketoprofen is well known to evoke the allergic type of photocontact dermatitis when it is applied to the skin and irradiated with ultraviolet A (UVA) light.


OBJECTIVE
We aimed to establish a murine model of this photosensitivity and to characterize pathogenic T cells concerned with the sensitivity.


METHODS
Various strains of mice were sensitized on two consecutive days by application of ketoprofen to the shaved abdomen and irradiation of the skin with UVA. Five days later, they were elicited with ketoprofen plus UVA on the earlobes. Immune lymph node cells and epidermal cells from the challenged sites were analyzed by RT-PCR.


RESULTS
Mice were successfully sensitized and challenged with 4% and 2% ketoprofen, respective, plus UVA at 20J/cm2. The responses in H-2k mice were higher than those in the other strains examined. Immune lymph node CD4+ or CD8+ cells from ketoprofen-photosensitized H-2k mice were transferred i.v. to naïve syngeneic recipients. Mice receiving CD4+ but not CD8+ cells exhibited ketoprofen photosensitivity, but transference of both CD4+ and CD8+ cell populations was more effective. Lymph node cells from photosensitized mice expressed high levels of mRNA for Th2 cytokine (IL-4) and Th2 chemokine receptor (CCR4) as well as Th1 cytokine (IFN-gamma) and Th1 chemokine receptor (CXCR3), as assessed by RT-PCR. In addition, epidermal cells from challenged earlobes expressed increased levels of both Th1 (TARC) and Th2 (Mig) chemokines.


CONCLUSIONS
It is considered that not only Th1 but also Th2 cells participate in the pathogenesis of murine photocontact dermatitis to ketoprofen.
Imai
Satoshi
S
Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Atarashi
Kenji
K
Ikesue
Koichi
K
Akiyama
Katsuhiko
K
Tokura
Yoshiki
Y
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics; D016827:CD8 Antigens / Q000032:analysis / Q000235:genetics; D017454:Dermatitis, Photoallergic / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007660:Ketoprofen / Q000009:adverse effects*; D008198:Lymph Nodes / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology / Q000528:radiation effects; D018418:Th2 Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D015704:CD4 Antigens; D016827:CD8 Antigens; C515355:Ccr4 protein, mouse; C515188:Cxcr3 protein, mouse; D012333:RNA, Messenger; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007371:Interferon-gamma; D007660:Ketoprofen