A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma.
Interleukin 4 (IL-4) is essential for the switching of B cells to IgE antibody production and for the maturation of T helper (Th) cells toward the Th2 phenotype. These mechanisms are thought to play a crucial role in the pathogenesis of the allergic airway inflammation observed in asthma. In the present study, we examined the anti-inflammatory effects of DNA administration of murine IL-4 mutant Q116D/Y119D (IL-4 double mutant, IL-4DM), which binds to the IL-4 receptor alpha and is an antagonist for IL-4. Immunization of BALB/c mice with alum-adsorbed ovalbumin (OVA) followed by aspiration with aerosolized OVA resulted in the development of allergic airway inflammation. A single administration of IL-4DM DNA before the aerosolized OVA challenge protected the mice from the subsequent induction of allergic airway inflammation. Serum IgE level and extent of eosinophil infiltration in bronchoalveolar lavage (BAL) from IL-4DM DNA-administered mice were significantly lower than those in BAL from control plasmid-immunized mice. In our study, IL-4 or IL-4 mutants were not detected in sera from mice that had received a single administration of IL-4DM DNA. The results of this study provide evidence for the potential utility of IL-4 mutant antagonist DNA inoculation as an approach to gene therapy for asthma.
Nishikubo
K
K
Third Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan.
Murata
Y
Y
Tamaki
S
S
Sugama
K
K
Imanaka-Yoshida
K
K
Yuda
N
N
Kai
M
M
Takamura
S
S
Sebald
W
W
Adachi
Y
Y
Yasutomi
Y
Y
D000818:Animals; D001249:Asthma / Q000628:therapy*; D001985:Bronchial Provocation Tests; D001991:Bronchitis / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage*; D004804:Eosinophils / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D007073:Immunoglobulin E / Q000096:biosynthesis; D015847:Interleukin-4 / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D010047:Ovalbumin; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018418:Th2 Cells / Q000378:metabolism; D019444:Vaccines, DNA
D016207:Cytokines; D012333:RNA, Messenger; D019444:Vaccines, DNA; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; D004247:DNA