Mandarapu Rajesh, Ajumeera Rajanna, Venkatesan Vijayalakshmi, Prakhya Balakrishna Murthy
International Institute of Biotechnology and Toxicology, Kancheepuram District, Padappai, Tamil Nadu 601301, India.
National Institute of Nutrition (ICMR), Jamai Osmania, Hyderabad, Telagana 500 007, India.
J Toxicol. 2014;2014:308286. doi: 10.1155/2014/308286. Epub 2014 Sep 18.
In recent times, human cell-based assays are gaining attention in assessments of immunomodulatory effects of chemicals. In the study here, the possible effects of cypermethrin and mancozeb on lymphocyte proliferation and proinflammatory (tumor necrosis factor (TNF-) α) and immunoregulatory cytokine (interferon- (IFN-) γ, interleukins (IL) 2, 4, 6, and 10) formation in vitro were investigated. Human peripheral blood mononuclear cells (PBMC) were isolated and exposed for 6 hr to noncytotoxic doses (0.45-30 µM) of cypermethrin or mancozeb in the presence of activating rat S9 fraction. Cultures were then further incubated for 48 or 72 hr in fresh medium containing phytohemagglutinin (10 µg/mL) to assess, respectively, effects on cell proliferation (BrdU-ELISA method) and cytokine formation (flow cytometric bead immunoassays). Mancozeb induced dose-dependent increases in lymphocyte proliferation, inhibition of production of TNFα and the TH2 cytokines IL-6 and IL-10, and an increase in IFNγ (TH1 cytokine) production (at least 2-fold compared to control); mancozeb also induced inhibition of IL-4 (TH2) and stimulated IL-2 (TH1) production, albeit only in dose-related manners for each. In contrast, cypermethrin exposure did not cause significant effects on proliferation or cytokine profiles. Further studies are needed to better understand the functional significance of our in vitro findings.
近年来，基于人类细胞的检测方法在化学物质免疫调节作用的评估中受到关注。在本研究中，调查了氯氰菊酯和代森锰锌对体外淋巴细胞增殖以及促炎细胞因子（肿瘤坏死因子（TNF-）α）和免疫调节细胞因子（干扰素-（IFN-）γ、白细胞介素（IL）2、4、6和10）形成的可能影响。分离出人类外周血单个核细胞（PBMC），并在存在活化大鼠S9组分的情况下，将其暴露于非细胞毒性剂量（0.45 - 30 μM）的氯氰菊酯或代森锰锌中6小时。然后将培养物在含有植物血凝素（10 μg/mL）的新鲜培养基中进一步孵育48或72小时，分别以评估对细胞增殖（BrdU - ELISA法）和细胞因子形成（流式细胞术微珠免疫测定）的影响。代森锰锌诱导淋巴细胞增殖呈剂量依赖性增加，抑制TNFα以及TH2细胞因子IL - 6和IL - 10的产生，并增加IFNγ（TH1细胞因子）的产生（与对照相比至少增加2倍）；代森锰锌还诱导抑制IL - 4（TH2）并刺激IL - 2（TH1）的产生，尽管每种情况都仅呈剂量相关方式。相比之下，暴露于氯氰菊酯对增殖或细胞因子谱没有显著影响。需要进一步研究以更好地理解我们体外研究结果的功能意义。
