[Modulation of allergic airway inflammation by immunostimulatory DNA sequences in conjunction with an allergen in a murine model of asthma].
OBJECTIVE
To compare the suppressive effects of immunostimulatory sequences (ISS-DNA) alone or ISS-DNA in conjunction with ovalbumin (OVA) on airway inflammation in a mouse model of asthma.


METHODS
Thirty six female BALB/c mice were divided into 4 groups: group ISS (A), group ISS + OVA (B), group OVA (C) and group normal saline (D). Mice in groups A, B and C were sensitized and challenged with OVA. Group A and group B were subdivided into subgroup A(1) and B(1) (injected intraperitoneally with ISS DNA 100 micro g or ISS DNA 100 micro g and OVA 10 micro g once) and subgroup A(2) and B(2) (injected intraperitoneally with ISS DNA or ISS DNA and OVA twice). Blood samples were obtained every week for six weeks. OVA-specific IgE was measured by ELISA. Bronchoalveolar lavage fluid (BALF), lung tissues and spleen cells were collected. BAL total cell numbers and differentials were counted. Interferon gamma (IFN-gamma) produced by OVA-stimulated spleen cells was determined by ELISA.


RESULTS
Eosinophil count in group A(1) [(2.39 +/- 0.81) x 10(4)/ml], group A(2) [(2.62 +/- 0.77) x 10(4)/ml], group B(1) [(1.80 +/- 0.12) x 10(4)/ml], and group B(2) [(1.84 +/- 0.67) x 10(4)/ml] were significantly lower than those in group C [(12.43 +/- 2.13) x 10(4)/ml], P < 0.05. The levels of IFN-gamma in group A(1) [(510 +/- 102) pg/ml], group A(2) [(492 +/- 98) pg/ml], group B(1) [(532 +/- 120) pg/ml], and group B(2) [(469 +/- 132) pg/ml] were significantly higher than those in group C [(194 +/- 80) pg/ml], P < 0.05. The serum level of IgE in group B was significantly lower than that in group C in four weeks, but that in group A was not significantly different from that in group C. A second dose of ISS-DNA did not show additional effect as compared to the signal dose treatment.


CONCLUSIONS
ISS-DNA inhibited allergic airway inflammation in a murine model of asthma. ISS-DNA and OVA combination was more effective than ISS-DNA alone.
Jin
Meiling
M
Department of Respiratory Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Cai
Yingyun
Y
Yuan
Zhenghong
Z
Zheng
Lingjie
L
Ren
Tao
T
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004247:DNA / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000502:physiology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
D000276:Adjuvants, Immunologic; D000485:Allergens; D007371:Interferon-gamma; D010047:Ovalbumin; D004247:DNA