Studies on effectiveness of the Chinese medicine against intractable mycobacterial infection

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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