Interferon-gamma inductive effect of liposomes as an immunoadjuvant.
Adjuvant effect of liposomes was compared to that of aluminium hydroxide (Alum) using ovalbumin (OVA) as a model antigen, and the difference in adjuvanticity of liposomes from Alum has been evaluated on the basis of cytokine production. Both adjuvants enhanced the IgG levels, but a remarkable difference was observed in the production of IgG subclass; Alum enhanced IgG1 levels, and liposomes enhanced IgG2a, IG2b, and IG3 levels. Further, Alum enhanced antigen-specific IgE levels, whereas liposomes did not. To clarify the difference in adjuvant effect of these adjuvants, secretion of cytokines, especially interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) which regulate IgE production, was estimated ex vivo. Overnight culture of splenic cells obtained from mice immunized with liposomes encapsulating OVA elicits IFN-gamma secretion, but not IL-4 secretion. On the other hand, the production of both cytokines was elevated by the immunization with OVA-Alum complex. The results indicate that the difference of adjuvant activity between liposomes and Alum may come from the difference in the secretion of IL-4 and that, consequently, a different class of antibody response is developed. More importantly, negatively charged liposomes containing phosphatidylserine remarkably promoted IFN-gamma secretion compared to neutral liposomes.
Aramaki
Y
Y
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Suda
H
H
Tsuchiya
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D004563:Electrochemistry; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007369:Interferon Inducers / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008081:Liposomes / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D007074:Immunoglobulin G; D007369:Interferon Inducers; D008081:Liposomes; D015847:Interleukin-4; C041524:aluminum sulfate; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin