THE EFFECT OF GLUCOSAMINYLMURAMYL DIPEPTIDE INJECTION TO MICE ON THE COURSE OF TUBERCULOUS INFECTION AND IN-VITRO SUPEROXIDE ANION PRODUCTION

Immunotherapy as an adjunct to chemotherapy is of interest for optimiz ing therapeutic regimens for tuberculosis. In this context, we investi gated the influence and mode of action of glucosaminylmuramyl dipeptid e (GMDP) in mouse experimental models. Intermittent injections of GMDP to Mycobacterium tuberculosis-infected mice reduced the viable bacill i in the lungs, but increased the counts in the spleens at 16 weeks, b ut not at earlier harvests after infection. Injections of GMDP selecti vely ameliorated also in the lungs the spontaneous relapse of infectio n following chemotherapy. The mode of GMDP action was examined in resp ect of superoxide anion production. The O-2(-) production by phorbol m yristate-induced peritoneal macrophages in vitro was reduced by preinj ection of mice with 100 mu g Of GMDP. Notably, this outcome contrasts and can also override the previously known enhancing effect of MDP on O-2(-) production. The inhibitory activity of GMDP became even more pr onounced when testing macrophages from Mycobacterium bovis BCG-infecte d mice. However, these results do not explain readily the grounds for the contrasting effects of GMDP on the growth patterns of tubercle bac illi in the lungs and spleens. Although the observed effects on bacill ary counts have been modest, such action of GMDP could represent a ben eficial adjunct to suitably formulated chemotherapeutic regimens.