Studies on effectiveness of the Chinese medicine against intractable mycobacterial infection

我们研究了包括多种中药在内的免疫调节剂增强宿主对禽型分枝杆菌复合体(MAC)感染的抗菌作用。获得了以下研究结果。(1)毛不实赛辛托可增强巨噬细胞(Mφ)的抗MAC活性。然而，有45种中药对M-φS细胞内M-φ的抗M-φ活性的增强作用较弱，其他中药均未表现出明显的增强作用，说明大多数中药通过直接增强细胞内M-DNA和/或淋巴细胞的功能来增强M-DNA对细胞内MAC的抗菌活性。(2)除Kakkon-to外，各类型MφS产生的活性氧中间体均较弱。(3)MφS只在塑料井内用试验中药进行预处理时才有上述作用。因此，它是…更可能的是，MBST激活的M-φS在信号转导方式上存在显着差异，这种差异取决于细胞-基质黏附的强度。(4)用增强M-φ抗φ活性的三磷酸腺苷联合MBST处理M-φS，并不显著增加M-φS产生的活性氮中间体.(5)刀豆蛋白A(ConA)诱导的T细胞有丝分裂反应可被Oenn-Gedoku-to和Hochu-Ekki-to显著抑制，但MBST的抑制作用弱于它们.另外17种中药对T细胞Con A有丝分裂无明显影响。(6)作为利用小干扰RNA调控M-φ功能的体外实验体系的第一步，我们研究了针对PD-L的反义寡核苷酸能否控制M-φ抑制活性。观察到φ特异性反义寡核苷酸在一定程度上降低了M-PDL抑制活性。(7)我们重点研究了天然有机产物吡啶甲酸(PA)作为一种免疫调节剂，其效果优于中药。我们发现PA增强了M-φ对胞内MAC的抗菌活性。PA可诱导Thp-1 MφS细胞发生早期凋亡，但不能诱导细胞出现中、晚期典型的DNA片段化。较少

We examined the effects of immunomodulating agents including various Chinese traditional medicines in potentiating of the host antimicrobial functions against Mycobacterium avium complex (MAC) infection. The following findings were obtained. (1) Mao-Bushi-Saishin-To (MBST) enhanced the macrophage (Mφ) anti-MAC activity. However, forty-five other Chinese traditional medicines did not exhibit such significant effects except for weak effect by Ma-Kyou-Yoku-Kan-To in potentiating anti-MAC activity of host Mφs. Thus, it appears that the efficacy in increasing of the Mφ antimicrobial activity against intracellular MAC by directly augmenting Mφ and/or lymphocyte functions is generally weak in case of most Chinese medicines. (2) The production of reactive oxygen intermediate (ROI) by various types of Mφs were weak induced by MBST treatment except for Kakkon-To. (3) These effects were found only when Mφs were pre-treated with test Chinese traditional medicine in plastic wells. Therefore, it is … More likely that there are significant differences in the mode of signal transduction in MBST-activated Mφs which depend on intensity of cell-matrix adhesion. (4) Treatment of Mφs with ATP, which potentiate Mφ anti-MAC activity, in combination with MBST did not significantly increase the production of reactive nitrogen intermediate by Mφs. (5) Concanavalin A (Con A)-induced T cell mitogenic responses were significantly inhibited by Ouren-Gedoku-To and Hochu-Ekki-To, while inhibitory efficacy of MBST was weaker than them. On the other hand, other 17 Chinese traditional medicines did not exhibit such effect on T cell Con A mitogenesis. (6) As the first step in the development of in vitro experimental systems to regulate various Mφ functions by using siRNA, we examined whether Mφ suppressor activity could be controlled by using antisense oligonucleotides specific to PD-L. There was observed the tendency that Mφ suppressor activity was decreased to some extent by the PDL-specific antisense oligonucleotides. (7) We focused on picolinic acid (PA), a natural organic product, as an immunomodulator better than Chinese traditional medicines. We found that PA potentiated Mφ antimicrobial activity against intracellular MAC. In addition, PA induced the early phase apoptotic events in THP-1 Mφs, without inducing DNA fragmentation characteristic to the middle to late phase apoptosis. Less