The
Chinese traditional medicine mao-bushi-saishin-to (MBST), which has anti-inflammatory effects and has been used to treat the
common cold and nasal
allergy in Japan, was examined for its effects on the therapeutic activity of a new
benzoxazinorifamycin,
KRM-1648 (KRM), against Mycobacterium avium complex (MAC)
infection in mice. In addition, we examined the effects of MBST on the anti-MAC activity of murine peritoneal macrophages (M phi s). First, MBST significantly increased the anti-MAC therapeutic activity of KRM when given to mice in combination with KRM, although MBST alone did not exhibit such effects. Second, MBST treatment of M phi s significantly enhanced the KRM-mediated killing of MAC bacteria residing in M phi s, although MBST alone did not potentiate the M phi anti-MAC activity. MBST-treated M phi s showed decreased levels of reactive
nitrogen intermediate (RNI) release, suggesting that RNIs are not decisive in the expression of the anti-MAC activity of such M phi populations. MBST partially blocked the
interleukin-10 (IL-10) production of MAC-infected M phi s without affecting their
transforming growth factor beta (
TGF-beta)-producing activity. Reverse transcription-PCR analysis of the lung tissues of MAC-infected mice at weeks 4 and 8 after
infection revealed a marked increase in the levels of
tumor necrosis factor alpha,
gamma interferon (IFN-gamma),
IL-10, and
TGF-beta mRNAs. KRM treatment of infected mice tended to decrease the levels of the test
cytokine mRNAs, except that it increased
TGF-beta mRNA expression at week 4. MBST treatment did not affect the levels of any
cytokine mRNAs at week 8, while it down-regulated
cytokine mRNA expression at week 4. At week 8, treatment of mice with a combination of KRM and MBST caused a marked decrease in the levels of the test
cytokines mRNAs, especially
IL-10 and IFN-gamma mRNAs, although such effects were obscure at week 4. These findings suggest that down-regulation of the expression of
IL-10 and
TGF-beta is related to the combined
therapeutic effects of KRM and MBST against MAC
infection.