Polarized TH1 responses by liposome-entrapped allergen and its potential in immunotherapy of allergic disorders

Abstract

Background: The conventional immunotherapy used for treating allergic individuals may at times lead to varying degrees of anaphylactic reaction. Liposomes have been proposed as a vehicle for safe and effective allergen-specific immunotherapy as multiple injections of liposome-entrapped allergen (LEA) have been shown to reduce specific IgE response and induce specific IgG response in BALB/c mice. Objective and methods: To elucidate the effect of LEA on polarization of T-cell responses, its effect on the relative production of TH1/TH2 type cytokines (namely IL-2, IL-4 and IFN-γ by commercially available ELISA kits and immunoglobulin profile as measured by ELISA) were studied. Histamine release on challenge of immunized mice was measured to examine the efficacy of LEA in preventing anaphylactic reactions. Results: Measurement of cytokine levels in serum and spleen cell culture supernatants of BALB/c mice injected repeatedly with either free allergen (FA) or LEA (three mice per group) indicate that LEA preferentially induces a TH1-type of response dominated by IFN-γ and IL-2 production. Further, it was also shown that immunization of mice with FA or LEA and subsequent challenge with a large dose of the sensitizing allergen leads to fatal systemic reactions in 50-65% of the animals treated with FA, whereas no mortality was observed in mice injected with LEA. Analysis of IgG subclasses in sera of mice immunized with LEA revealed a sixfold higher production of IgG1 antibodies than mice immunized with FA. Serum IgG2a, IgG2b, IgG3 and IgM responses were also enhanced in the group of mice immunized with LEA in comparison with mice injected with FA. Conclusion: The results indicate that LEA confers protection against anaphylaxis to mice due to their ability to induce a high IFN-γ :IL-4 ratio which may lead to decreased synthesis of IgE and reduced histamine release on challenge with FA.