阿维菌素原药对昆明小鼠免疫功能的影响

目的探讨阿维菌素原药对昆明小鼠细胞免疫功能、体液免疫功能和非特异性免疫功能的影响。方法阿维菌素设3个剂量组20、10、5mg/kg和阴性对照组,连续给昆明小鼠染毒28d;T淋巴细胞增殖和迟发型变态反应（DTH）检测细胞免疫功能;抗体生成细胞数（PFC）和半数溶血值（HC50）测定检测体液免疫功能;腹腔巨噬细胞吞噬鸡红细胞、碳粒廓清试验和NK细胞活性测定检测非特异性免疫功能。结果 20mg/kg组小鼠T淋巴细胞增殖能力为0.76（阴性对照为0.86）,HC50为128.45（阴性对照为140.96）,PFC为89.21×106（阴性对照为113.33×106）;20和10mg/kg组碳廓清吞噬指数分别为5.59、5.61（阴性对照为7.96）,鸡红细胞吞噬指数分别为0.86、0.90（阴性对照为1.05）,以上结果均比阴性对照组明显降低,且差异有统计学意义﹙P〈0.01﹚。结论阿维菌素原药对昆明小鼠在细胞免疫功能、体液免疫功能和非特异性免疫功能方面均有抑制作用。     

铅致小鼠睾丸DNA损伤与细胞增殖

目的研究慢性铅染毒对小鼠睾丸细胞毒性机制。方法应用单细胞凝胶电泳技术（SCGE），检测铅对雄性小鼠生殖细胞DNA损伤，四甲基偶氮噻唑蓝（MTT）实验检测睾丸细胞增殖功能，生化试剂检测细胞脂质过氧化损伤。结果从低剂量组到高剂量组铅均可引起睾丸生殖细胞DNA不同程度损伤；低（0．15％）、中（0．3％）、高（0．6％）DNA迁移长度及迁移率与对照组之间差异有统计学意义（P〈0．01）；中、高浓度铅具有抑制睾丸细胞增殖的作用，使睾丸丙二醛（MDA）升高、超氧化物歧化酶（SOD）、谷胱苷肽过氧化物酶（GSH-Px）活性降低。结论铅可致睾丸细胞脂质过氧化损伤，导致DNA链断裂损伤，且具有抑制睾丸细胞增殖作用。     

锂和锌及硒对小鼠细胞免疫功能的影响

目的 探讨微量元素锂、锌、硒对小鼠细胞免疫功能的影响。方法 应用灌胃法测定锂、锌、硒对小鼠胸腺、脾脏重量的影响,应用淋巴细胞增殖试验、E-花环形成试验、巨噬细胞吞噬功能测定试验,检测锂、锌、硒对小鼠细胞免疫功能的影响。结果 锂、锌、硒均可促进胸腺、脾脏增长,明显提高小鼠E-花环形成率、淋巴细胞增殖反应,亦可提高小鼠巨噬细胞吞噬百分率及吞噬指数。各实验组之间无明显差异。结论 适量的锂、锌、硒可明显提高小鼠外周T淋巴细胞数目,并可增强其应答能力,从而增强小鼠的细胞免疫功能。     

五氯酚钠急性染毒对小鼠免疫细胞损伤影响

目的观察五氯酚钠对小鼠细胞免疫、体液免疫和巨噬细胞功能的毒性作用。方法将五氯酚钠以25,50和100mg/kg经灌胃方式一次给予小鼠,然后观察给药后3,24和48h小鼠各项免疫功能的变化,采用T淋巴细胞增殖法测定细胞免疫功能,采用B淋巴细胞增殖法测定体液免疫功能,采用巨噬细胞吞噬能力和分泌NO的能力来测定巨噬细胞功能。结果100mg/kg五氯酚钠染毒后3h,小鼠的脾脏和胸腺相对重量较对照组降低,脾脏B淋巴细胞的增殖能力受到抑制,腹腔巨噬细胞的吞噬功能和NO生成能力受到抑制。25和50mg/kg五氯酚钠在染毒后24 h依然对脾细胞中B淋巴细胞增殖能力产生抑制作用。这种抑制效应到48h时完全消失。结论五氯酚钠一次染毒在25～100 mg/kg剂量范围内对小鼠体液免疫和细胞免疫功能产生抑制作用,100mg/kg对巨噬细胞功能产生抑制作用,对细胞免疫功能未见影响。     

噪声对小鼠细胞免疫功能的影响

为研究噪声对免疫系统的影响,模拟噪声作业环境强度特点,采用免疫毒理学方法,对暴露在１０５ｄＢ（ Ａ） 、９０ｄＢ（ Ａ） 、７５ｄＢ（Ａ） 噪声环境中的小鼠部分细胞免疫功能进行测定。结果表明：接噪组小鼠淋巴细胞增殖功能显著低于对照组,且有随噪声强度增加,细胞增殖功能降低的趋势。而细胞因子白细胞介素２ 的活性未见有明显变化。初步判定噪声对小鼠的免疫功能有一定的抑制作用     

铅对小鼠睾丸组织脂质过氧化作用及杭白菊对其保护作用的研究

本文通过给雄性小鼠腹腔注射醋酸铅染毒,测定各不同染毒剂量组与空白对照及杭白菊灌胃组中血铅、血浆中VitC和小鼠睾丸组织中T—SOD、GSH—Px活力,MDA含量．以观察铅对小鼠睾丸组织脂质过氧化作用及杭白菊对其保护作用。结果表明：铅染毒组T—SOD活力和GSH—Px活力下降．其中T—SOD活力与铅含量呈负相关（r＝-0．6098,P＜0．01）;杭白菊灌胃组T—SOD和GSH—Px活力上升,与铅染毒组相比,差异显著（P＜0．05）,其中GSH—Px恢复到对照水平。杭白菊灌胃组较染毒组血铅含量下降,血浆中VitC含量上升,差异显著（P＜0．05）。     

铅和乙醇对雄性大鼠生殖系统的联合毒作用

采用整体动物实验方法,观察铅和乙醇对大鼠精子数量和质量,以及血中性激素水平的联合作用。结果显示,精子计数联合组比铅和乙醇单独作用组显著减少;精子活动度分析联合组与其他各组比较显著下降。铅和乙醇单独作用均可使雄性大鼠血清睾酮(T)升高,促黄体生成激素(LH)下降,联合作用使T降低,LH较单独作用组升高。提示铅和乙醇联合染毒对雄性大鼠生殖毒性影响可能具有增毒作用。     

镉对小鼠淋巴细胞增殖功能、IL-2影响与cAMP的关系

目的：观察镉对小鼠脾T淋巴细胞增殖功能、cAMP(环磷酸腺苷)、IL-2(白细胞介素-2)等的影响，探讨它们在镉的免疫毒性中作用和关系。方法：对BALB／C小鼠体外、体内染镉后，测定脾T淋巴细胞增殖功能、IL-2活性、cAMP含量等。结果：体内、体外染镉均引起了小鼠脾T淋巴细胞增殖功能、IL-2水平有剂量一效应关系的降低，两者的变化呈正直线相关。体内染镉引起IL-2水平对数的降低与cAMP水平的升高呈负直线相关。体外染镉引起T淋巴细胞增殖功能、IL-2水平的降低与cAMP水平升高呈负直线相关。结论：镉有抑制小鼠脾T淋巴细胞IL-2活性的免疫毒性作用；IL-2在镉抑制T淋巴细胞增殖活性中有重要作用；cAMP信使系统可能参与介导了镉对脾T淋巴细胞增殖功能、IL-2.     

骨碎补醇提物对免疫抑制小鼠细胞免疫功能的调节作用

目的研究骨碎补乙醇提取物对环磷酰胺诱导的免疫抑制小鼠细胞免疫功能的调节作用。方法 60只昆明种小鼠随机分为6组:空白对照组,低下模型组,阳性对照组(左旋咪唑0.05 g/kg),骨碎补醇提物低、中、高剂量组(2.5、5和10 g/kg),每组10只。4个给药组按10 m L/kg容积灌胃给药20 d,空白对照组和低下模型组给予等体积的生理盐水。除空白对照组外,其余5组小鼠于给药的第11~13天腹腔注射80 mg/kg环磷酰胺建立免疫抑制模型。实验结束后,检测小鼠脾淋巴细胞增殖能力,迟发型超敏反应,脾组织病理切片,外周血T淋巴细胞亚群CD_4~+、CD_8~+T细胞数,脾组织IFN-γ、IL-4 mRNA的表达等指标。结果 5 g/kg和10 g/kg骨碎补醇提物可以增强小鼠刀豆蛋白A诱导的脾脏T淋巴细胞增殖能力、迟发型超敏反应(DTH),提高外周血CD4+T细胞数、CD_4~+/CD_8~+比值、脾组织IFN-γmRNA的表达以及IFN-γ/IL-4比值;可以降低外周血CD_8~+T细胞数以及脾组织IL-4 mRNA的表达;但对脂多糖诱导的B淋巴细胞增殖反应无明显影响。结论骨碎补醇提物对环磷酰胺诱导的免疫抑制小鼠的细胞免疫功能有调节作用。     

十溴联苯醚对雌性小鼠免疫毒性的初步研究

目的探讨十溴联苯醚(decabromodiphenyl ether,BDE-209)对小鼠免疫系统的毒性作用。方法将120只健康SPF级未妊娠雌性BALB/c小鼠分为三批,每批按体重随机分为4组,分别为阴性对照(花生油)组和低(20 mg/kg)、中(100 mg/kg)、高(500 mg/kg)剂量BDE-209染毒组,每组10只。采用经口灌胃方式进行染毒,染毒容量为0.01 ml/g,每天1次,连续染毒30 d。测定淋巴细胞增殖情况、NK细胞活性、血清半数溶血值(HC50)、腹腔巨噬细胞吞噬功能。结果与阴性对照组比较,仅100、500 mg/kg BDE-209染毒组小鼠T淋巴细胞增殖功能明显降低,差异均有统计学意义(P<0.05);各剂量BDE-209染毒组小鼠NK细胞活性、血清HC50、吞噬百分率和吞噬指数均无显著变化。结论 BDE-209可降低小鼠T淋巴细胞增殖能力,对小鼠细胞免疫功能具有抑制的作用。     

The effect of controlled ozone exposure on human lymphocyte function

The effects of ozone (O₃) on cell-mediated immunity were studied in 16 human subjects exposed to 1176 μg/m³ O₃ (0.6 ppm) for 2 hr in an environmentally controlled exposure chamber. Venous blood samples were taken before and immediately after controlled air and O₃ exposures, as well as at 72 hr, 2 and 4 weeks, and at one random time at least 1 month after treatment. The relative frequency of T lymphocytes in blood and the in vitro blastogenic response of lymphocytes to phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and Candida albicans were determined. During the course of the experiment, no statistically significant changes were observed in the number of T lymphocytes that form spontaneous rosettes with sheep erythrocytes. The response of T lymphocytes to PHA was significantly reduced (P < 0.05) in samples taken at 2 and 4 weeks following O₃ exposure. Normal response to PHA was observed at 2 months post-O₃ exposure. No statistically significant changes in lymphocyte responses to Con A. PWM, or Candida were seen. These results show that one 2 hr exposure of humans to 0.6 ppm O₃ may lead to a transient suppression of the PHA-stimulated blastogenic transformation of peripheral blood lymphocytes. The data indicate that the blastogenic response to PHA of human lymphocytes is exquisitely sensitive to O₃ exposure and could serve as a bioassay for evaluating subtle changes in cellular immunity induced by O₃ and possibly other pollutants.     

Mitogen response of B cells, but not T cells, is impaired in adult vitamin A-deficient rats

The effect of vitamin A deficiency on the mitogen response of splenic B and T lymphocytes was determined in adult vitamin A-deficient rats. Female weanling Brown Norway/Billingham-Rijswijk (BN/BiRij) and Sprague-Dawley rats were fed a semipurified, essentially vitamin A-free diet, which resulted in clinical symptoms of vitamin A deficiency and severely decreased plasma retinol contents at the age of about 17 and 41 wk for BN/BiRij and Sprague-Dawley rats, respectively. A lower B cell proliferative response after stimulation with lipopolysaccharide in combination with dextran sulfate was observed in vitamin A-deficient rats of both strains, but the T cell proliferative response after concanavalin A stimulation was unchanged. The lower B cell mitogen response was not associated with changes in the cellular composition of the spleen (as analyzed with monoclonal antibodies specific for the various subsets of T and B cells and of macrophages). We suggest that the age at which clinical symptoms of vitamin A deficiency are induced may be an important determinant for the immunological variables affected.     

L-carnitine enhances lymphocyte mitogenesis in depleted traumatised and infected patients

The influence of L-carnitine on concanavalin (ConA)-induced lymphocyte mitogenesis in vitro was studied in six depleted patients with severe post-operative infections and in eight healthy control subjects. Three patients had received i. v. carnitine supplementation as part of a clinical trial. One patient was studied both before and after i.v. carnitine supplementation. Five patients showed a poor or absent mitogen response compared with the controls. Carnitine markedly augmented the mitogen response in all these patients. In the patient studied before and after i. v. carnitine supplementation, the low initial ConA response increased to values seen in normal individuals. In the lymphocytes from healthy control subjects, no effect of carnitine on activation could be observed.The results demonstrate a stimulatory effect of L-carnitine on lymphocyte mitogenesis in depleted patients with severe post-operative infections.     

维生素E对辐照小鼠胸腺、脾淋巴细胞数及脾淋巴细胞转化反应的影响

小鼠分别饲以基础饲料及基础饲料添加维生素E50mg/kg和500mg/kg饲料4周。然后一次全身照射400radX线,分别于照射后第6天,第14天处死,计脾与胸腺细胞数并测定脾淋巴细胞转化反应。结果表明:基础饲料组小鼠脾和胸腺细胞数较维生素E添加组明显减少(P<0.01);维生素E添加组小鼠脾T、B淋巴细胞转化反应较基础饲料组明显增高(P<0.01),且高剂量维生素E添加组的T淋巴细胞转化反应亦显著高于低剂量组(P<0.01)。     

Effects of excessive dietary zinc on the intrauterine and postnatal development of mink

Dietary exposure to 1000 ppm of supplemental Zn did not result in grossly observable Zn toxicity or Zn-induced Cu deficiency in adult mink. These same concentrations did, however, produce achromatrichia, alopecia, lymphopenia and a reduced rate of growth in the offspring produced by the Zn-treated females. These mink kits also exhibited profound immunosuppression. The in vitro blastogenic response of peripheral blood lymphocytes to concanavalin A was significantly (P less than 0.001) lower in kits born to Zn-treated dams than the response of those born to control dams. The depressed immunoresponsiveness was not a permanent defect since a normal lymphocyte response was seen approximately 14 weeks after weaning and being placed on an unsupplemented basal diet. The impaired lymphocyte reactivity is believed to be the result of altered DNA synthesis in these cells and/or an inhibition of macrophage functions necessary for normal response to the mitogen concanavalin A.     

Immunoglobulin and cytokine production from spleen lymphocytes is modulated in C57BL/6J mice by dietary cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid

We evaluated the effect of cis-9, trans-11 (9c,11t) and trans-10, cis-12 (10t,12c) conjugated linoleic acid (CLA) on the immune system in C57BL/6J mice. Mice were fed experimental diets containing 0% CLA (controls), 1% 9c,11t-CLA, 1% 10t,12c-CLA or a 1:1 mixture (0.5% + 0.5%) of these two CLA isomers for 3 wk. Relative spleen weights of all CLA fed mice were greater than the controls. Spleen lymphocytes isolated from the mice fed 10t,12c-CLA produced more immunoglobulin (Ig)A and IgM but not IgG when stimulated with concanavalin A (ConA) compared with controls. IgA production from unstimulated spleen lymphocytes was greater in the 10t, 12c-CLA group than in controls. Conversely, 9c,11t-CLA did not affect the production of any of the Ig subclasses. Lymphocytes isolated from 9c,11t-CLA fed mice produced more tumor necrosis factor-alpha than the control group. The proportion of B cells in the spleen lymphocyte population was significantly lower in the 9c,11t-CLA group, and higher in the 10t,12c-CLA group than in the controls. Compared with the control group, the percentage of CD4(+) T cells was lower in the 10t,12c-CLA group, and the percentage of CD8(+) T cells was higher in the 9c,11t-CLA group. Furthermore, the percentage of CD8(+) T cells was higher in the 1:1 mixture group than in controls. The CD4(+)/CD8(+) ratio was lower in the 1:1 mixture group than in controls. These results suggest that 9c,11t and 10t,12c-CLA can stimulate different immunological effects and that the simultaneous intake of the two isomers can change the T cell population.     

Protein malnutrition alone and in combination with endotoxin impairs systemic and gut-associated immunity.

Because protein-malnourished or endotoxemic patients are at an increased risk of developing nosocomial infections, this study was performed to investigate the effects of protein malnutrition and endotoxemia, alone and in combination, on systemic and intestinal immunity. Protein malnutrition was created by feeding the animals a solid diet containing 0.03% protein. Subgroups of these protein-malnourished mice were killed after being challenged with saline or endotoxin on days 0, 7, 14, or 21. At death, the animals were weighed, tissues were harvested for histologic analysis (ileum, mesenteric lymph node [MLN], liver, and spleen), mitogen responsiveness (MLN, Peyer's patches, and spleen), and xanthine oxidase measurements (ileum and cecum). Separate groups were evaluated for survival. Both the saline and endotoxin-challenged mice had lost about 30% of their body weight after 21 days on the low-protein diet. The protein-malnourished mice were more susceptible to endotoxin-induced mortality (70% at 21 days) than the normally nourished mice (0%) (p less than .001). The mitogen responsiveness of the protein-malnourished mice to the T-cell mitogens (PHA and Con-A) progressively decreased the longer the mice were protein malnourished, and this decreased in blastogenic responsiveness was associated with histologic evidence of lymphoid atrophy. In contrast, the blastogenic response to the primarily B-cell mitogen, PWM, was largely preserved. The endotoxin challenge further depressed the immune state of mice tested after 0, 7, or 14 (but not 21) days of protein malnutrition. Thus, both protein malnutrition and endotoxin impaired systemic and gut-associated immune responsiveness to mitogens. However, in the protein-malnourished mice, the degree of immune suppression did not correlate with endotoxin-induced mortality.     

Protection of mice and guinea pigs against tuberculosis induced by immunization with a single Mycobacterium tuberculosis recombinant antigen, MTB41

MTB41 is a Mycobacterium antigen that is recognized by CD4+ T cells early after experimental infection of mice with Mycobacterium tuberculosis and by PBMC from healthy PPD positive individuals. Immunization of mice with plasmid DNA encoding the MTB41 gene sequence results in the development of antigen-specific CD4+ and CD8+ T cells, and protection against challenge with virulent M. tuberculosis. In the present studies, in contrast to DNA immunization, we show, that a strong MTB41-specific CD4+ T cell response, but no MHC class I restricted cytotoxic T lymphocyte (CTL) activity is detected in the spleen cells of infected mice. Therefore, this data suggests that the induction of CD8+ T cell response to MTB41 epitopes by DNA immunization may not be relevant to protection because these epitopes are not recognized during the infectious process. We also compared the repertoire of rMTB41 epitope recognition by CD4+ T cells of M. tuberculosis-infected mice with the recognition repertoire of mice immunized with the recombinant rMTB41 protein. Both regimens of sensitization lead to the recognition of the same molecular epitope. Coincidentally, immunization with the soluble recombinant protein plus adjuvant, a regimen known to generate primarily CD4+ T cells, resulted in induction of protection comparable to BCG in two well-established animal models of tuberculosis (mice and guinea pigs).     

Impairment of blastogenic response of splenic lymphocytes from iron-deficient mice: in vivo repletion

Iron-deficiency anemia impaired the blastogenic response of splenic lymphocytes and partially purified T cells to Concanavalin A and phytohemagglutinin. The response of splenic lymphocytes and partially B cells to bacterial lipopolysaccharide was also significantly impaired. Caloric restriction in pair-fed mice did not have any significant effect. Blastogenic response to the three mitogens was restored to normal after anemic mice were fed the regular diet containing 25 to 30 mg Fe/kg (FeSO4) for approximately 10 days. We also found that in the anemic mice the mean wet weights per 100 g of body of spleen, heart, brain, and kidney increased, while those of the thymus and liver decreased. In the pair-fed mice only the mean wet weight of the liver significantly decreased. There was a small but significant decrease in the white blood count and peripheral lymphocyte count in the anemic but not the pair-fed mice. The mechanism by which iron deficiency impairs the cell-mediated immune response is discussed.     

RRR‐α‐Tocopheryl succinate inhibition of lectin‐induced T cell proliferation

The effect of RRR‐α‐tocopheryl succinate (VES) on lectin‐induced chicken T cell proliferation was investigated. The T cell mitogens concanavalin A and phytohemagglutinin induce chicken thymic and splenic T cell proliferation. Addition of VES to the in vitro cultures inhibited T cell proliferation in a dose‐dependent manner. Addition of VES to spleen cell cultures at different times after mitogen stimulation also suppressed T cell mitogenesis, suggesting that VES is not mediating its antiproliferative effects by interfering with ligand (mitogen)‐receptor binding or early ligand‐bound receptor‐signaling events. Three lines of evidence suggest that the growth‐inhibitory properties of VES are unique and may not involve antioxidant properties. 1) Three other forms of vitamin E, dl‐α‐tocopherol, d‐α‐tocopherol, and d‐α‐tocopherol acetate, do not inhibit the proliferation of mitogen‐stimulated chicken spleen cells. 2) Spleen cells were treated with an inhibitor of nonspecific esterases to prevent the conversion of VES, which does not exhibit antioxidant properties to d‐a‐tocopherol, a lipid‐soluble antioxidant. Treatment of spleen cells with the inhibitor did not affect VES's growth‐inhibitory properties. 3) Trolox, a water‐soluble vitamin E analogue with potent antioxidant properties and two Hpid‐soluble antioxidants, butylated hydroxyanisole and butylated hydroxytoluene, did not inhibit mitogen‐induced T cell proliferation. Attempts to reverse VES's antiproliferative effects by addition of exogenous interleukin‐2 or addition of sodium selenite, an enhancer of interleukin‐2 receptors, failed. Acetylsalicylic acid had no effect on VES's inhibition of mitogen‐activated T cell proliferation. These studies support the role of VES as a growth inhibitor of lectin‐activated normal T cells in chickens.