Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, 37 S. P. Mukherjee Road, Kolkata, India.
Int Immunopharmacol. 2013 Jan;15(1):73-83. doi: 10.1016/j.intimp.2012.11.006. Epub 2012 Nov 21.
We have evaluated the toxicity profile of a unique immunomodulator, neem leaf glycoprotein (NLGP) on different physiological systems of Swiss mice and Sprague Dawley rats. NLGP injection, even in higher doses than effective concentration caused no behavioral changes in animals and no death. NLGP injection increased the body weights of mice slightly without any change in organ weights. NLGP showed no adverse effect on the hematological system. Moreover, little hematostimulation was noticed, as evidenced by increased hemoglobin content, leukocyte count and lymphocyte numbers. Histological assessment of different organs revealed no alterations in the organ microstructure of the NLGP treated mice and rats. Histological normalcy of liver and kidney was further confirmed by the assessment of liver enzymes like alkaline phosphatase, SGOT, SGPT and nephrological products like urea and creatinine. NLGP has no apoptotic effect on immune cells but induces proliferation of mononuclear cells collected from mice and rats. Number of CD4(+), CD8(+) T cells, DX5(+) NK cells, CD11b(+) macrophages and CD11c(+) dendritic cells is upregulated by NLGP without a significant change in CD4(+)CD25(+)Foxp3(+) regulatory T cells. Type 1 cytokines, like IFNγ also increased in serum with a decrease in type 2 cytokines. Total IgG content, especially IgG2a increased in NLGP treated mice. These type 1 directed changes help to create an anti-tumor immune environment that results in the restriction of carcinoma growth in mice. Accumulated evidence strongly suggests the non-toxic nature of NLGP. Thus, it can be recommended for human use in anti-cancer therapy.
我们评估了印苦楝叶糖蛋白（NLGP）对瑞士小鼠和 Sprague Dawley 大鼠不同生理系统的毒性概况。NLGP 注射，即使在高于有效浓度的剂量下，也不会引起动物行为改变或死亡。NLGP 注射略微增加了小鼠的体重，而器官重量没有变化。NLGP 对血液系统没有不良影响。此外，如血红蛋白含量、白细胞计数和淋巴细胞数量增加所示，注意到轻微的血液刺激作用。不同器官的组织学评估显示，NLGP 处理的小鼠和大鼠的器官微观结构没有改变。碱性磷酸酶、SGOT、SGPT 等肝酶和尿素、肌酐等肾产物的评估进一步证实了肝脏和肾脏的组织学正常。NLGP 对免疫细胞没有凋亡作用，但诱导从小鼠和大鼠收集的单核细胞增殖。NLGP 上调 CD4(+)、CD8(+) T 细胞、DX5(+)NK 细胞、CD11b(+)巨噬细胞和 CD11c(+)树突状细胞的数量，而 CD4(+)CD25(+)Foxp3(+)调节性 T 细胞没有显著变化。血清中 1 型细胞因子（如 IFNγ）增加，2 型细胞因子减少。NLGP 治疗的小鼠总 IgG 含量，特别是 IgG2a 增加。这些 1 型定向变化有助于创造抗肿瘤免疫环境，从而导致小鼠癌生长受限。大量证据强烈表明 NLGP 的非毒性。因此，它可以推荐用于人类癌症治疗。
