The Effect of Glucosaminylmuramyl Dipeptide Injection to Mice on the Course of Tuberculous Infection and in vitro Superoxide Anion Production

摘要

Immunotherapy as an adjunct to chemotherapy is of interest for optimizing therapeutic regimens for tuberculosis. In this context, we investigated the influence and mode of action of glucosaminylmuramyl dipeptide (GMDP) in mouse experimental models. Intermittent injections of GMDP to Mycobacterium tuberculosis-infected mice reduced the viable bacilli in the lungs, but increased the counts in the spleens at 16 weeks, but not at earlier harvests after infection. Injections of GMDP selectively ameliorated also in the lungs the spontaneous relapse of infection following chemotherapy. The mode of GMDP action was examined in respect of superoxide anion production. The O––/sup>2 production by phorbol myristate-induced peritoneal macrophages in vitro was reduced by preinjection of mice with 100 μg of GMDP. Notably, this outcome contrasts and can also override the previously known enhancing effect of MDP on O––/sup>2 production. The inhibitory activity of GMDP became even more pronounced when testing macrophages from Mycobacterium bovis BCG-infected mice. However, these results do not explain readily the grounds for the contrasting effects of GMDP on the growth patterns of tubercle bacilli in the lungs and spleens. Although the observed effects on bacillary counts have been modest, such action of GMDP could represent a beneficial adjunct to suitably formulated chemotherapeutic