アルコールによるIMMUNE CIRCUIT増幅作用の解析

Abstract

In order to acquire a better understanding of the precise mechanism of elevated serum IgA levels in patients with alcoholic liver diseases, the author investigated effects of alcohol (AL) on the immune circuit in C57BL/6 (high AL preference) mice and DBA/2 (low AL preference) mice. Short-term administration of AL elicited polyclonal antibody production in C57BL/6 mice, but not in DBA/2 mice. Long-term oral administration of AL, however, elicited polyclonal antibody production in the spleen and Peyer's patch of DBA/2 mice as well as C57BL/6 mice. When sheep red blood cells (SRBCs) were administered as an antigen, intraperitoneal injection of SRBCs induced stronger anti-SRBC responses than oral administration in both mice. After 1 month oral administration of AL, however, differences of anti-SRBC responses were not observed between intraperitoneal and oral administration. Moreover, after 4 months oral administration of AL, oral administration of SRBCs caused stronger anti-SRBC responses than intraperitoneal administration. Thus, long-term oral administration of AL altered the degree of immune responses that was caused by the difference of administration routes of the antigen. These results suggest that AL increased the permeability of antigens in the intestinal mucosal layer. Furthermore, it was demonstrated that long-term oral administration of AL activated T-cells and macrophages, and increased both Interleukin-1 and Interleukin-2 activity. These results indicate that AL acts as a low-molecular-weight polyclonal B-cell activator, and enhances polyclonal antibody production in the gut-associated lymphoid tissue such as Peyer's patch. Therefore, it is suggested that AL enhances the immune circuit, resulting in the increase of serum IgA levels in patients with alcoholic liver diseases.