Topical suplatast tosilate (IPD) ameliorates Th2 cytokine-mediated dermatitis in caspase-1 transgenic mice by downregulating interleukin-4 and interleukin-5.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by elevated serum levels of IgE. AD is associated with Th2 cytokines including interleukin (IL)-4, IL-5, IL-13 and IL-10. Systemic administration of suplatast tosilate (IPD) is currently used to treat Th2 cytokine-mediated AD.


OBJECTIVE
To evaluate the effect of topical IPD on skin lesions of AD using a genetically engineered AD mouse model (K14/caspase-1 transgenic mouse: KCASP1Tg).


METHODS
IPD ointment (3%) and white petrolatum (WP) were applied to KCASP1Tg mice every other day from 6 to 14 weeks after birth. Histopathological analysis of skin lesions and measurement of mRNA expression of cytokines in skin lesions and spleen cells were carried out. We also compared changes in serum parameters between IPD-treated and WP-treated KCASP1Tg mice.


RESULTS
WP-treated mice developed dermatitis at 8 weeks after birth. However, skin lesions in IPD-treated mice were limited. Histopathologically, skin lesions in WP-treated KCASP1Tg mice showed marked inflammatory changes with increased mast cell infiltration. However, mice treated with IPD showed minimum skin lesions with scarce mast cell infiltration. WP-treated KCASP1Tg mice had significant elevation in the serum levels of histamine, IgE and IL-18 as compared with IPD-treated KCASP1Tg mice. mRNA expression of IL-4 and IL-5 in the skin lesions from WP-treated KCASP1Tg mice was significantly higher than in those from IPD-treated mice. In the spleen, the expression of IL-4, IL-5 and interferon-gamma was significantly increased in WP-treated KCASP1Tg mice as compared with their IPD-treated counterparts.


CONCLUSIONS
This study shows that topical therapy with IPD inhibits the expression of IL-4 and IL-5 and ameliorates skin manifestations in an AD mouse model, suggesting the potential usefulness of topical IPD for the treatment of AD.
Murakami
T
T
Department of Dermatology, Mie University, Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
Yamanaka
K
K
Tokime
K
K
Kurokawa
I
I
Tsutsui
H
H
Nakanishi
K
K
Mizutani
H
H
D000287:Administration, Topical; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001190:Arylsulfonates / Q000008:administration & dosage* / Q000627:therapeutic use; D020170:Caspase 1 / Q000235:genetics; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015536:Down-Regulation; D006632:Histamine / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology; D013452:Sulfonium Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D018418:Th2 Cells / Q000276:immunology
D018926:Anti-Allergic Agents; D001190:Arylsulfonates; D015848:Interleukin-5; D012333:RNA, Messenger; D013452:Sulfonium Compounds; D015847:Interleukin-4; D007073:Immunoglobulin E; D006632:Histamine; D007371:Interferon-gamma; C073028:suplatast tosilate; D020170:Caspase 1