Effect of Tilorone Treatment on Intracellular Microbial Infections in Specific-Pathogen-Free Mice

Abstract

Specific-pathogen-free CD-1 mice were treated orally with the drug tilorone (2,7-bis[2-diethylaminoethoxy]fluoren-9-one hydrochloride) at dosages of 10 or 100 mg per kg of body weight. Drug was given 24 h before challenge and then every other day for up to 15 days. Growth of sublethal doses of Listeria monocytogenes, Mycobacterium bovis (BCG Montreal), M. tuberculosis H37Rv, and Salmonella enteritidis in the livers and spleens of intravenously challenged mice was significantly increased compared with that in control animals receiving distilled water orally. Tilorone given every other day at a dosage of 10 mg/kg reduced (but did not completely ablate) the tuberculin response to the mycobacterial infections. Both tuberculin hypersensitivity and anti-mycobacterial resistance returned to normal values within days of stopping the drug treatment. Tilorone treatment at the 100-mg/kg dose level increased the growth of S. enteritidis in both intravenously and intragastrically challenged mice; this effect seemed to be due to the reduced ability of the host to express the normal granulomatous response to the microbial infection within the liver and spleen.