Effects of suramin on the in vivo antimicrobial resistance against Listeria monocytogenes and Mycobacterium bovis (BCG) in mice.

Following one intraperitoneal injection of Suramin (400 mg/kg) in mice, biphasic alterations of the resistance to Listeria monocytogenes were observed, depending on the timing of the drug administration in relation to the intravenous challenge. Treatment with suramin, concomitantly or 1 day before, enhanced markedly the bacterial growth in spleen and liver, detected as early as 3 to 6 h after the challenge, the maximum being observed at 48 h in the liver. In contrast, an increased resistance was observed when suramin was given 8 days before the challenge. This late effect was associated with a stimulation of the mononuclear phagocyte system as measured by the increase of the spleen index and accumulation of histiocytic cells in the lymphoid organs, such as peripheral nodes. Intraperitoneal inoculation of suramin (100 mg/kg), before, during and after an intravenous injection of low dose (2 X 10(4)/mouse) of Mycobacterium bovis (BCG) in C57BL/6 and CH3 mice were followed, in both strains, by a similar increase of the mycobacterial growth in spleen and liver during the first 2 weeks. This indicates that suramin was acting on a different non specific mechanism of resistance than the one being expressed by the Bcg gene controlling the natural resistance as described recently. However, when the same schedule of suramin treatment was given to these two strains, during subcutaneous immunization with 1 X 10(7) viable BCG, a significant decrease of 48 h delayed-type hypersensitivity to tuberculin was noted 21 days later only in C57BL/6 but not in C3H mice, in which such a reaction was also of low magnitude in the infected control. The decrease of this cell-mediated immunity parameter in C57BL/6 suramin treated mice was also correlated with a higher number of viable BCG found at the challenge site and in the draining nodes.