Bhakuni V, Kulkarni S, Ali V, Singh U K, Levy H B, Maheshwari R K
Division of Membrane Biology, Central Drug Research Institute, Lucknow, India.
J Interferon Cytokine Res. 1999 Oct;19(10):1103-6. doi: 10.1089/107999099313037.
We demonstrate that golden hamsters infected with Leishmania donovani amastigotes develop the capacity to eliminate intracellular pathogens on treatment with low-dose standard antileishmanial sodium stibogluconate (Stibanate) in combination with polyinosinic-polycytidilic acid stabilized with polylysine and carboxymethycellulose (poly ICLC), a potent inducer of interferon (IFN) and immune enhancer, plus L-arginine. Data suggest that low doses of both Stibanate and poly ICLC plus L-arginine provide marginal inhibition against L. donovani infection in golden hamsters. When given in combination, however, a significant inhibition was achieved without toxicity, as all the animals survived up to 45 or 60 days. These results suggest that combination therapy using Stibanate and poly ICLC plus L-arginine may be very effective in reducing the dose of Stibanate and, hence, its dose-dependent toxicity in clinical situations.
我们证明,感染杜氏利什曼原虫无鞭毛体的金黄仓鼠在接受低剂量标准抗利什曼药葡萄糖酸锑钠(斯锑黑克)与聚肌苷酸-聚胞苷酸(用聚赖氨酸和羧甲基纤维素稳定,即聚ICLC,一种有效的干扰素诱导剂和免疫增强剂)加L-精氨酸联合治疗后,获得了消除细胞内病原体的能力。数据表明,低剂量的斯锑黑克和聚ICLC加L-精氨酸对金黄仓鼠的杜氏利什曼原虫感染仅提供边际抑制作用。然而,当联合使用时,在无毒性的情况下实现了显著抑制,因为所有动物都存活到了45天或60天。这些结果表明,使用斯锑黑克和聚ICLC加L-精氨酸的联合疗法在临床情况下可能非常有效地降低斯锑黑克的剂量,从而降低其剂量依赖性毒性。