Maw W W, Tomioka H, Sato K, Saito H
Department of Microbiology and Immunology, Shimane Medical University, Izumo, Japan.
Int J Lepr Other Mycobact Dis. 1997 Sep;65(3):345-51.
In the present study, we evaluated the in vivo anti-Mycobacterium leprae activities of KRM-1648 (KRM) given at long intervals in combination with ofloxacin (OFLX), clofazimine (CFZ), and dapsone (DDS). We also examined the combined effects of two biological response modifiers (BRMs), gamma interferon (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF), on the therapeutic efficacy of KRM. KRM exhibited potent therapeutic efficacy against M. leprae infection in mice even when given at 4-week intervals. KRM displayed increased efficacy in combination with OFLX, CFZ, and DDS (given three or six times per week) when given to mice in the multidrug combination KRM + OFLX + CFZ + DDS. The therapeutic efficacy of KRM given at 4-week intervals was increased by combined use with IFN-gamma but not by GM-CSF. Adoptive transfer of M. leprae antigen-primed lymphocytes of euthymic mice to recipient athymic nude mice with progressive M. leprae infection markedly enhanced host resistance.
在本研究中，我们评估了间隔较长时间给予的KRM-1648（KRM）与氧氟沙星（OFLX）、氯法齐明（CFZ）和氨苯砜（DDS）联合使用时对体内麻风分枝杆菌的活性。我们还研究了两种生物反应调节剂（BRM），即γ干扰素（IFN-γ）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）对KRM治疗效果的联合影响。即使以4周的间隔给药，KRM对小鼠的麻风分枝杆菌感染仍表现出强大的治疗效果。当以多药联合KRM + OFLX + CFZ + DDS给予小鼠时，KRM与OFLX、CFZ和DDS（每周给药三次或六次）联合使用时显示出更高的疗效。与IFN-γ联合使用可提高间隔4周给予的KRM的治疗效果，但与GM-CSF联合使用则无此效果。将麻风分枝杆菌抗原致敏的正常小鼠淋巴细胞过继转移到患有进行性麻风分枝杆菌感染的无胸腺裸鼠受体中，可显著增强宿主抵抗力。
