DNA vaccination against macrophage migration inhibitory factor improves atopic dermatitis in murine models.
BACKGROUND
Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has been implicated in the pathogenesis of AD. Recently, we developed a novel DNA vaccine that generates neutralizing endogenous anti-MIF antibodies.


OBJECTIVE
This study explores the preventive and therapeutic effects of this MIF-DNA vaccine in mouse models of AD.


METHODS
Two different AD model mice (DS-Nh and NC/Nga) received MIF-DNA vaccination to analyze preventive and therapeutic effects, as assessed by clinical skin scores, histologic findings, and serum IgE levels.


RESULTS
In murine models of AD, MIF-DNA vaccination prevented the occurrence of the AD skin phenotype. Furthermore, administration of MIF-DNA vaccine to mice that had already developed AD produced a rapid improvement in AD skin manifestation. There were reduced histologic signs of inflammation and lower serum IgE levels in treated mice compared with those seen in control animals. Finally, passive transfer of IgG from MIF-DNA vaccinated mice to AD mice also produced a significant therapeutic effect. These results demonstrate that MIF-DNA vaccination not only prevents the development of AD but also improves the symptoms of pre-existing AD.


CONCLUSIONS
Taken together, the induction of an anti-MIF autoantibody response using MIF-DNA vaccination appears to be a useful approach in the treatment of AD.
Hamasaka
Asuka
A
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Abe
Riichiro
R
Koyama
Yoshikazu
Y
Yoshioka
Naoya
N
Fujita
Yasuyuki
Y
Hoshina
Daichi
D
Sasaki
Mikako
M
Hirasawa
Tsutomu
T
Onodera
Shin
S
Ohshima
Shigeki
S
Leng
Lin
L
Bucala
Richard
R
Nishihira
Jun
J
Shimizu
Tadamichi
T
Shimizu
Hiroshi
H
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013744:Tetanus Toxin / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019444:Vaccines, DNA / Q000627:therapeutic use*
D001323:Autoantibodies; D008263:Macrophage Migration-Inhibitory Factors; D013744:Tetanus Toxin; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D007073:Immunoglobulin E