IL-6 acts as a key cytokine in the augmentation of mucosal immunity following intranasal administration of antigen with liposomes

Research Project

Project/Area Number	22590073
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Biological pharmacy
Research Institution	Tokyo University of Pharmacy and Life Science
Principal Investigator	ARAMAKI Yukihiko 東京薬科大学, 薬学部, 教授 (90138959)
Co-Investigator(Kenkyū-buntansha)	NEGISHI Yoichi 東京薬科大学, 薬学部, 准教授 (50286978)
Project Period (FY)	2010 – 2012
Project Status	Completed (Fiscal Year 2012)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2010: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords	リポソーム / 粘膜ワクチン / アジュバント / IL-6 / ナノキャリアー / アジュバンド
Research Abstract	The mucosal immune system acts as a first line of defense against infection caused by luminal pathogens. To deliver antigen and mucosal adjuvants to nasopharynx-associated lymphoid tissue (NALT) effectively is an important for the development of mucosal immunity. In this study, we examined the activation mechanism of mucosal immunity following intranasal administration of antigen in combination with cationic liposomes composed of DOTAP and DC-cholesterol (DC-Chol). Intranasal administration of OVA with cationic liposomes induced higher levels of mucosal IgA and systemic IgG. Antigen specific IgA level was the same to that of mice which were immunized with OVA and cholera toxin. Uptake of OVA in NALT DC was enhanced by DOTAP/DC-Chol as carrier. Furthermore, DOTAP/DC-Chol enhanced the production of IL-6, an important cytokine for the induction of antigen-specific mucosal IgA, in the nasal passage. Pre-treatment of mice with anti-IL-6R antibody suppressed the production of IgA to the control levels. The antibody treatment decreased CD138+ and IgA+B220+ cell populations which have been up-regulated in nasal passage by nasal administration of OVA with CpG-ODN and cationic liposomes. These findings strongly suggested that intranasal administration of antigen with CpG-ODN and cationic liposomes induced mucosal immunity, and IL-6 could act as an important cytokine for the augmentation of mucosal immune response. Recently, GM-CSF was strongly suggested the contribution in the production IL-6 following intranasal administration of OVA and the cationic liposomes composed of DOTAP/DC-Chol.