Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
PLoS One. 2011;6(7):e22188. doi: 10.1371/journal.pone.0022188. Epub 2011 Jul 22.
Streptococcus pyogenes (S. pyogenes) causes various serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. One serious problem observed recently with S. pyogenes therapy is attenuation of the antibiotic effect, especially penicillin treatment failure and macrolide resistance. Hainosankyuto, a traditional Japanese medicine based on ancient Chinese medicine, has been used for treatment of infectious purulent diseases in Japan. In this study, we investigated the protective and therapeutic efficacy of Hainosankyuto against S. pyogenes-skin infection.
METHODOLOGY/PRINCIPAL FINDINGS: A broth microdilution method revealed that Hainosankyuto did not show a direct anti-bacterial effect against S. pyogenes. Force-feeding Hainosankyuto to infected mice for 4 consecutive days increased the survival rate and reduced the size of local skin lesions compared with mice fed PBS. Although we did not find the significant recovery of survival rate in Hainosankyuto administration only after S. pyogenes infection, the sizes of ulcer lesion were significant smaller after Hainosankyuto administration compared with mice fed PBS. No difference was observed in the anti-bacterial effect of Hainosankyuto between macrolide-susceptible and -resistant strains. Blood bactericidal assay showed that the survival rate of S. pyogenes using the blood from Hainosankyuto-treated mice was lower than that using the blood from untreated mice. We also found increased levels of IL-12, IFN-γ and a decreased level of TNF-α in the serum of S. pyogenes-infected mice treated with Hainosankyuto. Mouse peritoneal macrophage from Hainosankyuto-treated mice had significant phagocytic activity and increased mRNA levels of IL-12, IFN-γ and decreased mRNA level of TNF-α compared with control macrophage.
CONCLUSIONS/SIGNIFICANCE: Hainosankyuto increased survival rate after S. pyogenes infection and up-regulated both blood bactericidal activity and macrophage phagocytic activity through modulation of inflammatory cytokines. Our data also suggest Hainosankyuto may be useful for the treatment of S. pyogenes infection more prophylactically than therapeutically.
酿脓链球菌（S. pyogenes）可引起多种严重疾病，包括坏死性筋膜炎和链球菌中毒性休克综合征。最近观察到的酿脓链球菌治疗的一个严重问题是抗生素效果减弱，特别是青霉素治疗失败和大环内酯类耐药。汉方清肠汤是一种基于古中医的传统日本药物，已在日本用于治疗感染性化脓性疾病。在这项研究中，我们研究了汉方清肠汤对酿脓链球菌皮肤感染的保护和治疗效果。
方法/主要发现：肉汤微量稀释法显示汉方清肠汤对酿脓链球菌无直接抗菌作用。连续 4 天强迫感染小鼠服用汉方清肠汤可提高存活率并减少局部皮肤损伤的大小，与服用 PBS 的小鼠相比。虽然我们没有发现汉方清肠汤给药后在酿脓链球菌感染后对存活率的显著恢复，但汉方清肠汤给药后溃疡病变的大小明显小于服用 PBS 的小鼠。汉方清肠汤对大环内酯类敏感和耐药株的抗菌作用无差异。血液杀菌试验表明，使用汉方清肠汤处理的小鼠血液中的酿脓链球菌存活率低于未处理的小鼠。我们还发现，在汉方清肠汤治疗的酿脓链球菌感染小鼠的血清中，IL-12、IFN-γ水平升高，TNF-α水平降低。与对照巨噬细胞相比，来自汉方清肠汤处理的小鼠的腹膜巨噬细胞具有明显的吞噬活性，并且 IL-12、IFN-γ 的 mRNA 水平增加，TNF-α 的 mRNA 水平降低。
结论/意义：汉方清肠汤可提高酿脓链球菌感染后的存活率，并通过调节炎症细胞因子提高血液杀菌活性和巨噬细胞吞噬活性。我们的数据还表明，汉方清肠汤可能更适用于预防性治疗酿脓链球菌感染，而不是治疗性治疗。
