Wu Y, Cai D
Department of Immunology, Chinese Academy of Medical Sciences, Beijing.
Proc Soc Exp Biol Med. 1992 Dec;201(3):284-8. doi: 10.3181/00379727-201-43509.
The in vitro effect of lithium on lymphokine-activated killer cell (LAK) activity and its in vivo antitumor growth were observed. LAK activity was enhanced when LiCl was added during LAK cell induction, and this enhancement was observed both in human peripheral blood mononuclear cell and in mouse splenocytes used as LAK precursors. Cholera toxin, which can increase intracellular levels of cAMP, decreased LAK cell activity. However, lithium partially reversed this inhibitory effect, indicating that lithium increased LAK cell activity by decreasing cAMP levels. D-Sphingosine, an inhibitor of protein kinase C, and EGTA, a calcium chelator, both inhibited the LAK cell activity. However, their inhibitory effects could not be reversed by lithium because lithium was added in the culture in combination with one of these inhibitors during LAK cell induction. By using slot blot analysis, the effect of lithium on the expression of tumor necrosis factor-alpha mRNA of LAK cells was analyzed. Lithium increased the level of tumor necrosis factor-alpha mRNA when both lithium and interleukin 2 were added to induce LAK cells. The in vivo antitumor effect of lithium has also been studied. Using a mouse melanoma experimental model, the effect of lithium on tumor growth was also observed. Both lithium alone and interleukin 2/LAK had an antitumor effect, whereas the treatment of interleukin 2/LAK in combination with lithium had the strongest inhibitory effect on tumor growth, since this treatment resulted in reduction of tumor size and prolongation of survival in tumor-bearing mice. Therefore, it is hopeful that lithium can be used as a new immunomodulator for cancer immunotherapy and immune diseases.
观察了锂对淋巴因子激活的杀伤细胞（LAK）活性的体外作用及其体内抗肿瘤生长作用。当在LAK细胞诱导过程中添加LiCl时，LAK活性增强，并且在用作LAK前体的人外周血单个核细胞和小鼠脾细胞中均观察到这种增强。可增加细胞内cAMP水平的霍乱毒素降低了LAK细胞活性。然而，锂部分逆转了这种抑制作用，表明锂通过降低cAMP水平来增加LAK细胞活性。蛋白激酶C抑制剂D-鞘氨醇和钙螯合剂EGTA均抑制LAK细胞活性。然而，由于在LAK细胞诱导过程中锂与这些抑制剂之一联合添加到培养物中，它们的抑制作用不能被锂逆转。通过斑点印迹分析，分析了锂对LAK细胞肿瘤坏死因子-α mRNA表达的影响。当锂和白细胞介素2都添加用于诱导LAK细胞时，锂增加了肿瘤坏死因子-α mRNA的水平。还研究了锂的体内抗肿瘤作用。使用小鼠黑色素瘤实验模型，也观察了锂对肿瘤生长的影响。单独使用锂和白细胞介素2/LAK均具有抗肿瘤作用，而白细胞介素2/LAK与锂联合治疗对肿瘤生长具有最强的抑制作用，因为这种治疗导致荷瘤小鼠肿瘤大小减小和生存期延长。因此，有望将锂用作癌症免疫治疗和免疫疾病的新型免疫调节剂。
