Effect of the new immunostimulator HAB 439 on cell-mediated immunity against intracellular bacteria.

The isoxazoline derivative HAB 439 was tested for its enzyme inhibiting potency and was found to be an inhibitor of aminopeptidase B (IC50 = 22.5 micrograms/ml). In further immunopharmacological experiments its efficacy to stimulate cell-mediated immunity was evaluated. HAB 439 was shown to stimulate DTH-reaction against Salmonella typhimurium and Listeria monocytogenes. HAB 439 protected animals against infection by reducing the bacterial load in livers and spleens and by decreasing the mortality rate. Treatment with the antibiotic ampicillin induced a decreased DTH-reaction in mice which was demonstrated to be due to a reduction of the antigen to be presented to the immune system and not to immune suppression. HAB 439 restored the impaired immune response to S. typhimurium and L. monocytogenes in a dose-dependent way. Restoration of DTH was shown to lead to an improvement of protection in ampicillin-treated mice which were challenged with the intracellular bacteria.