Maeyama J, Isaka M, Yasuda Y, Matano K, Kozuka S, Taniguchi T, Ohkuma K, Tochikubo K, Goto N
Department of Safety Research on Biologics, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
Microbiol Immunol. 2001;45(2):111-7. doi: 10.1111/j.1348-0421.2001.tb01276.x.
We attempted to clarify the mechanism of the mucosal adjuvanticity of recombinant cholera toxin B subunit (rCTB), which is inherently uncontaminated with the holotoxin produced by Bacillus brevis and has a powerful mucosal adjuvant activity, on cytokine responses compared with that of cholera toxin (CT). rCTB had no ability to stimulate cyclic AMP formation in mouse peritoneal macrophages (Mphi). Cytokine production by non-immunized Mphi cultured with rCTB or CT and by the spleen cells of mice co-immunized intranasally with ovalbumin (OVA) and rCTB or CT was examined. rCTB alone did not induce interleukin (IL)-1alpha/beta or IL-6 production by Mphi, but combination of rCTB with lipopolysaccharide (LPS) enhanced both IL-1alpha/beta production. Conversely, CT plus LPS suppressed IL-1alpha/beta production more than LPS alone. Both rCTB and CT suppressed IL-12 secretion induced by interferon gamma (IFN gamma) plus LPS. IL-2, IL-4, IL-5, and IL-10 were secreted by mouse spleen cells restimulated with OVA after intranasal co-administration of OVA together with rCTB, and in response to CT, the same cytokines were secreted. The different effect of rCTB on Mphi from that of CT may mean a difference between the mechanisms of rCTB and CT during the early stage of an immune response.
我们试图阐明重组霍乱毒素B亚基（rCTB）的黏膜佐剂作用机制，rCTB天然不被短芽孢杆菌产生的全毒素污染，具有强大的黏膜佐剂活性，我们将其与霍乱毒素（CT）相比，研究其对细胞因子反应的影响。rCTB无法刺激小鼠腹腔巨噬细胞（Mphi）中环状AMP的形成。检测了用rCTB或CT培养的未免疫Mphi以及经鼻联合免疫卵清蛋白（OVA）与rCTB或CT的小鼠脾细胞产生细胞因子的情况。单独的rCTB不会诱导Mphi产生白细胞介素（IL）-1α/β或IL-6，但rCTB与脂多糖（LPS）联合使用可增强IL-1α/β的产生。相反，CT加LPS比单独的LPS更能抑制IL-1α/β的产生。rCTB和CT均抑制干扰素γ（IFNγ）加LPS诱导的IL-12分泌。经鼻联合给予OVA与rCTB后，用OVA再次刺激的小鼠脾细胞分泌IL-2、IL-4、IL-5和IL-10，对CT有反应时，也分泌相同的细胞因子。rCTB对Mphi的作用与CT不同，这可能意味着在免疫反应早期rCTB和CT的作用机制存在差异。
