Hübner L, Ernst M, von Laer D, Schwander S, Flad H D
Department of Immunology and Cell Biology, Forschungsinstitut Borstel, F.R.G.
Int J Immunopharmacol. 1991;13(8):1067-72. doi: 10.1016/0192-0561(91)90157-3.
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.
二乙基二硫代氨基甲酸盐（DTC）最近被报道可显著降低HIV感染患者机会性感染的发生率。本研究探讨了DTC是否能够刺激单核吞噬细胞的抗分枝杆菌活性这一问题。我们发现，健康受试者的外周血单核细胞（PBMC）在体外与100 - 1000 ng/ml的DTC预孵育，随后感染结核分枝杆菌H37Rv或鸟分枝杆菌 - 胞内分枝杆菌复合群，通过测定分枝杆菌集落形成单位评估，与对照孵育的细胞相比，其抗分枝杆菌活性增强。在随后的实验中，对注射了5 mg/kg体重DTC的健康志愿者的单核细胞在注射后的不同时间段进行了体外抗分枝杆菌活性测试。注射DTC导致抗分枝杆菌活性显著增强，在注射DTC后24小时最为明显。我们得出结论，DTC在体外和体内均可刺激单核吞噬细胞的抗菌功能。这些结果可能解释了在接受DTC治疗的HIV感染患者中观察到的良好临床病程，并可能为耐药非典型分枝杆菌病患者使用DTC治疗提供依据。
