Lipid A analogue, ONO-4007, inhibits IgE response and antigen-induced eosinophilic recruitment into airways in BALB/c mice.
BACKGROUND
Since antigen-specific IgE and eosinophils are major inducing factors of allergic inflammation of the airways, both factors are therapeutic targets of asthma. We investigated the effects of ONO-4007, a nontoxic lipid A analogue, on antigen-specific antibody response and the recruitment of eosinophils into airways in murine systems.


METHODS
BALB/c mice were injected ONO-4007 intraperitoneally during sensitization with ovalbumin (OVA) and aluminium hydroxide to determine its effects on the antigen-specific antibody response. ONO-4007 was also injected intravenously during either systemic sensitization and inhalation with OVA, or sensitization or inhalation alone to determine its effects on antigen-induced airway inflammation. In vitro effects of ONO-4007 on the functional differentiation of naive CD4+ T cells were investigated by culturing naive CD4+ T cells derived from DO11.10 mice and OVA-pulsed dendritic cells (CDCs) with ONO-4007.


RESULTS
ONO-4007 inhibited antigen-specific IgE and IgG1, but not IgG2a responses. ONO-4007 decreased the recruitment of eosinophils and the levels of IL-5 in bronchoalveolar lavage fluid, not only when it was injected during systemic sensitization and inhalation with OVA, but also during inhalation alone. ONO-4007 inhibited the differentiation of IL-4- and IL-13-producing CD4+ T cells in vitro, which was partly mediated by DCs.


CONCLUSIONS
ONO-4007 inhibited antigen-specific IgE and IgG1 responses and antigen-induced eosinophil recruitment into the airways in BALB/c mice. These effects were mediated, at least partly, by the modulation of DCs, although there may also be other mechanisms.
Iio
Jun
J
Department of Pediatrics, Graduate School of Medicine, Kyoto University, Japan.
Katamura
Kenji
K
Takeda
Hiroshi
H
Ohmura
Kayo
K
Yasumi
Takahiro
T
Meguro
Taka-aki
TA
Ohshima
Yusei
Y
Nakahata
Tatsutoshi
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000941:Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D008050:Lipid A; C086889:ONO 4007; D007073:Immunoglobulin E; D000536:Aluminum Hydroxide; D010047:Ovalbumin