Enhancement of monocyte antimycobacterial activity by diethyldithiocarbamate (DTC)

Abstract

Diethyldithiocarbamate (DTC) has been recently reported to significantly reduce the incidence of opportunistic infections in HIV-infected patients. The present study addresses the question whether DTC is capable of stimulating antimycobacterial activity of mononuclear phagocytes. We found that peripheral blood mononuclear cells (PBMC) of healthy subjects preincubated in vitro with 100-1000 ng/ml of DTC and thereafter infected with Mycobacterium tuberculosis H37Rv or Mycobacterium avium-intracellulare complex exhibited an enhanced antimycobacterial activity compared with control-incubated cells as assessed by the determination of mycobacterial colony-forming units. In subsequent experiments monocytes from healthy volunteers injected with 5 mg/kg body weight of DTC were tested ex vivo for antimycobacterial activity at various periods of time after injection. Injection of DTC resulted in a significant enhancement of antimycobacterial activity which was most evident 24 h after DTC injection. We conclude that DTC stimulates the antimicrobial function of mononuclear phagocytes both in vitro and in vivo. These results may explain the favourable clinical course observed in HIV-infected patients treated with DTC and may serve as a basis for treatment with DTC in patients with drug-resistant atypical mycobacteriosis.