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

Background The conventional immunotherapy used for treating allergic indivi duals may at times lead to varying degrees of anaphylactic reaction. Liposo mes have been proposed as a vehicle for safe and effective allergen-specifi c immunotherapy as multiple injections of liposome-entrapped allergen (LEA) have been shown to reduce specific IgE response and induce specific IgG re sponse in BALB/c mice. Objective and methods To elucidate the effect of LEA on polarization of T-c ell responses, its effect on the relative production of TH1/TH2 type cytoki nes (namely IL-2, IL-4 and IFN-gamma by commercially available ELISA kits a nd immunoglobulin profile as measured by ELISA) were studied. Histamine rel ease 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 sup ernatants of BALB/c mice injected repeatedly with either free allergen (FA) or LEA (three mice per group) indicate that LEA preferentially induces a T H1-type of response dominated by IFN-gamma and IL-2 production. Further, it was also shown that immunization of mice with FA or LEA and subsequent cha llenge with a large dose of the sensitizing allergen leads to fatal systemi c 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 ant ibodies than mice immunized with FA. Serum IgG2a, IgG2b, IgG3 and IgM respo nses were also enhanced in the group of mice immunized with LEA in comparis on with mice injected with FA. Conclusion The results indicate that LEA confers protection against anaphyl axis to mice due to their ability to induce a high IFN-gamma:IL-4 ratio whi ch may lead to decreased synthesis of IgE and reduced histamine release on challenge with FA.