Lipid A Analogue, ONO-4007, Inhibits IgE Response and Antigen-Induced Eosinophilic Recruitment into Airways in BALB/c Mice

Abstract

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 IgG_2a 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.