瑞舒伐他汀和阿托伐他汀在急性冠脉综合症中对氯吡格雷抗血小板活性的对比研究

目的：在急性冠脉综合征（acute coronary syndromes,ACS）的治疗中,抗血小板治疗及调脂治疗是最基础的治疗方案。近来有学者提出,氯吡格雷和他汀类药物都经过细胞色素CYP3A4途径代谢,二者因存在竞争性抑制,有可能降低氯吡格雷抗血小板的活性。本试验将针对阿托伐他汀及瑞舒伐他汀进行研究。方法：选择急性冠脉综合症的患者42例,所有患者均接受氯吡格雷治疗（负荷剂量300mg,维持剂量75mg／d）。随机分配为A、B两组,A组（n=20）服用阿托伐他汀治疗（20mg／d）,B组（n=22服用瑞舒伐他汀治疗（10mg／d）。分别于氯吡格雷服用前、服药治疗后3天、服药治疗后7天后采静脉血送检,测定ADP（10μmol／L）诱导的血小板聚集率。结果：阿托伐他汀组（A组）及瑞舒伐他汀组（B组）相比,服用氯吡格雷前ADP诱导的血小板聚集率基线值无统计学差异。服用氯吡格雷3日及7日后,ADP诱导的血小板聚集率明显降低,（3．85±2．58）vs（3．09±2．27）,（0．65±0．88）vs（1．05±0．95）,P〉0．05,无明显统计学差异。结论：氯吡格雷的确可以降低血小板的活性。同时,短期之内氯吡格雷的抗血小板活性未受到他汀类的影响。包括经过CPY3A4途径的他汀,如阿托伐他汀。     

瑞舒伐他汀和阿托伐他汀在急性冠脉综合症中对氯吡格雷抗血 小板活性的对比研究

目的：在急性冠脉综合征( acute coronary syndromes, ACS )的治疗中,抗血小板治疗及调脂治疗是最基础的治疗方案。近来 有学者提出,氯吡格雷和他汀类药物都经过细胞色素CYP 3A4 途径代谢,二者因存在竞争性抑制,有可能降低氯吡格雷抗血小板 的活性。本试验将针对阿托伐他汀及瑞舒伐他汀进行研究。方法：选择急性冠脉综合症的患者42 例,所有患者均接受氯吡格雷治 疗（负荷剂量300 mg,维持剂量75 mg/d）。随机分配为A、B 两组,A 组（n=20）服用阿托伐他汀治疗（20 mg/d）,B 组（n=22 服用瑞 舒伐他汀治疗（10 mg/d）。分别于氯吡格雷服用前、服药治疗后3 天、服药治疗后7 天后采静脉血送检,测定ADP（10 滋mol/L）诱导 的血小板聚集率。结果：阿托伐他汀组（A 组）及瑞舒伐他汀组（B 组）相比,服用氯吡格雷前ADP 诱导的血小板聚集率基线值无 统计学差异。服用氯吡格雷3 日及7 日后,ADP诱导的血小板聚集率明显降低,(3.85± 2.58)vs(3.09± 2.27),(0.65± 0.88)vs(1.05± 0.95),P>0.05,无明显统计学差异。结论：氯吡格雷的确可以降低血小板的活性。同时,短期之内氯吡格雷的抗血小板活性未受到 他汀类的影响,包括经过CPY3A4途径的他汀,如阿托伐他汀。     

Highly deoxynivalenol contaminated oats and immune function in horses

The aim of the present study was to investigate the impact of deoxynivalenol (DON) on cellular and humoral immune parameters in horses. A feeding trial using naturally contaminated oats with high (20.2 mg/kg) and low (0.49 mg/kg) levels of DON was conducted. Two groups of five mares were fed 2 kg oats daily with high or low DON levels for two weeks, using a crossover design with a three-week wash-out period. No adverse effects on general health were observed. Only minor diet-related changes in differential blood counts and serum biochemistry were noted. Serum haptoglobin concentration was significantly elevated after feeding DON (p = 0.04). Lymphocyte subsets (CD4+ CD8+, CD2+, CD21+, MHCII+) and lymphocyte proliferation data (concanavalin A, phytohemagglutinin, pokeweed mitogen) were not different between feeding-groups. It can be concluded that daily DON intakes as high as 6.9 to 9.5 mg/100 kg BW appear to have no major impact on the measured immune response of horses, indicating that this species has a high tolerance for DON.     

Suppression of mitogen-induced lymphocyte proliferation by syringomycin-E

Abstract Syringomycin E (SR-E) is low molecular weight bacterial lipodepsipeptide with antifungal properties. Owing to immunosuppressive activities of such compounds as cyclosporine, FK506 and rapamycin, we studied the effect of SR-E on proliferation of human blood lymphocytes in vitro. SR-E, by itself, had no effect but the mitogen-induced lymphocyte proliferation was significantly suppressed. The suppressive effect was more pronounced with pokeweed mitogen (PWM) as compared to phytohemagglutinin (PHA) or monoclonal antibody to CD3 (anti-CD3). Since these mitogens induce cellular immunity (T cell-dependent), SR-E may potentially be a novel immunosuppressive compound.     

Effects of a β3-adrenergic agonist on the immune response in diet-induced (cafeteria) obese animals

Molecules with affinity for beta3-adrenoceptors are not only effective anti-obesity agents in rodent models, but may play a role in the regulation of the immune response. The aim of the current investigation was to analyse the effects of trecadrine on the immune response in diet-induced (cafeteria) obese rats. Male Wistar rats were divided into 2 groups, the control group (C, n=9) was fed with the standard pelleted chow laboratory diet, while the other group was fed with a high-fat (cafeteria) diet. Cafeteria-fed rats were divided into two new subgroups (n=9 each), which received either i.p. saline (obese, O) or trecadrine (1mg/kg/day) (obese+trecadrine, O+T) daily for 5 weeks. Lymphocyte subpopulations and the proliferative response were determined by validated procedures. The administration of trecadrine was able to prevent the onset of obesity in cafeteria-fed rats. Trecadrine-treatment to obese animals appeared to improve the number of lymphocyte subpopulations (CD4+ and CD8+) as compared to those animals only receiving the high-fat diet, being the values of the trecadrine-treated animals on the high-fat diet similar to the control rats. However, the lymphoproliferative response when stimulated with several mitogens was markedly reduced by the cafeteria intake and was further decreased by the beta3-adrenergic administration. The spleen mRNA expression level of UCP2, PPARgamma and Ob-Rb were not affected by the trecadrine treatment. Summing up, at the immune system level, trecadrine administration increased the proportion of CD4+ spleen lymphocytes, although it was not able to restore the lymphocyte proliferative response which was depressed.     

Hemorrhage produces abnormalities in lymphocyte function and lymphokine generation

Hemorrhage has been shown to produce abnormalities in lymphocyte function, particularly in the proliferative response to mitogens such as PHA and Con A. In order to better examine the hemorrhage-induced alterations in immune function, we determined the effects of blood loss in mice without any surgical manipulation on lymphocyte populations and subpopulations, cellular activation, and lymphokine production. Hemorrhage induced no changes in cell numbers in the spleen, thymus, lymph nodes, and bone marrow. No alterations in the relative percentages of B (B220+, mu+) and T (Lyt-1+, Lyt-2+, T3+, L3T4+) cell subpopulations were found in any organ after blood loss. Significant decreases in splenocyte proliferation in response to Con A, IL-2R expression and blast formation occurred after hemorrhage. IFN-gamma production increased 24 and 48 h post hemorrhage. Decreases in IL-2, IL-3, and IL-5 generation were present 2 h after blood loss. IL-2 production remained significantly decreased for 48 h posthemorrhage, then increased to more than twice normal levels 72 h posthemorrhage, and subsequently returned to prehemorrhage values. These results demonstrate that hemorrhage produces widespread alterations in immune function without affecting lymphocyte population and subpopulation numbers.     

Cell numbers and in vitro responses of leucocytes and lymphocyte subpopulations following maximal exercise and interval training sessions of different intensities.

In vitro lymphocyte function and the mobilisation of peripheral blood leucocytes was examined in eight trained subjects who undertook an incremental exercise test to exhaustion and a series of interval training sessions. Venous blood samples were obtained before the incremental test, immediately after, and 30, 60, and 120 min after the test. Interval training sessions were undertaken on separate days and the exercise intensities for each of the different sessions were 30%, 60%, 90% and 120% of their maximal work capacity respectively, as determined from the incremental exercise test. There were 15 exercise periods of 1-min duration separated by recovery intervals of 2 min in each session. Venous blood samples were obtained immediately after each training session. Significant increases in lymphocyte subpopulations (CD3+, CD4+, CD8+, CD20+, and CD56+) occurred following both maximal and supramaximal exercise. This was accompanied by a significant decrease in the response of cultures of peripheral blood lymphocytes to Concanavalin A (ConA), a T-cell mitogen. The state of lymphocyte activation in vivo as measured by CD25+ surface antigen was not, however, affected by acute exercise. The total number of lymphocytes, distribution of lymphocyte subpopulations and in vitro lymphocyte response to ConA had returned to pre-exercise levels within half an hour of termination of exercise but serum cortisol concentrations had not begun to fall at this time. There was a significant decrease in the CD4+:CD8+ cell ratio following exercise; this was more the result of increases in CD3-CD8+ cells (CD8+ natural killer cells) than to CD3+CD8+ cells (CD8+ T-lymphocytes). Decreased responsiveness of T-cells to T-cell mitogens, postexercise, may have been the result of decreases in the percentage of T-cells in postexercise mixed lymphocyte cultures rather than depressed cell function. The cause of this was an increase in the percentage of natural killer cells which did not respond to the T-cell mitogen. The results indicated that while a substantial immediate in vitro "immunomodulation" occurred with acute exercise, this did not reflect an immunosuppression but was rather the result of changes in the proportions of reactive cells in mononuclear cell cultures. We have also demonstrated that the degree of the change in distribution of lymphocyte subpopulation numbers and responsiveness of peripheral blood mononuclear cells in in vitro mitogen reactions increased with increasing exercise intensity. Plasma volume changes may have contributed to some of the changes seen in leucocyte population and subpopulation numbers during and following exercise.     

Effect of hindlimb suspension simulation of microgravity on in vitro immunological responses

The effects of microgravity on the immune system are largely unknown, but understanding such effects becomes increasingly important as space exploration continues and mission duration increases. Reductions in postflight human T cell reactivity to mitogens is well documented. Similar results have been obtained using a clinostat as an in vitro model of microgravity. In this study, a rat tail suspension model of weightlessness was used to examine in vitro lymphocyte proliferation in response to mitogens. Experiments were designed to uncover potential deficits in events related to proliferation including cell surface protein and IL-2 receptor (IL-2R) expression, interleukin-2 (IL-2) production, and accessory cells. Suspension of rats for 1 week led to a significant depression in [3H]thymidine incorporation by mitogen-stimulated peripheral blood lymphocytes (PBL) but only a small decrease in the proliferation of lymph node lymphocytes and splenocytes. There were no changes in the percentages of cells expressing CD4, CD5, CD8 or immunoglobulin. Moreover, no changes in IL-2 production or IL-2R expression were observed. More esterase-positive macrophages were detected in all lymphatic tissues of suspended rats, but there was no corresponding increase in the percentage of cells bearing the macrophage markers OX41 or OX42. This increase in the number of macrophages may be related to the observed suppression of lymphocyte proliferation. The tissue specificity of the decrease in mitogen activation indicates that there may be a compartmentalized response in the rats tested in the hindlimb suspension model.     

Hypergravity-induced immunomodulation in a rodent model: lymphocytes and lymphoid organs

The major goal of this study was to quantify changes in lymphoid organs and cells over time due to centrifugation-induced hypergravity. C57BL/6 mice were exposed to 1, 2 and 3 G and the following assays were performed on days 1, 4, 7, 10, and 21: spleen, thymus, lung, and liver masses; total leukocyte, lymphocyte, monocyte/macrophage, and granulocyte counts; level of splenocyte apoptosis; enumeration of CD3+ T, CD3+/CD4+ T helper, CD3+/CD8+ T cytotoxic, B220+ B, and NK1.1+ natural killer cells; and quantification of cells expressing CD25, CD69, and CD71 activation markers. The data show that increased gravity resulted in decreased body, spleen, thymus, and liver, but not lung, mass. Significant reductions were noted in all three major leukocyte populations (lymphocytes, granulocytes, monocyte/macrophages) [correction of macrphages] with increased gravity; persistent depletion was noted in blood but not spleen. Among the various lymphocyte populations, the CD3+/CD8+ T cells and B220+ B cells were the most affected and NK1.1+ NK cells the least affected. Overall, the changes were most evident during the first week, with a greater influence noted for cells in the spleen. A linear relationship was found between some of the measurements and the level of gravity, especially on day 4. These findings indicate that hypergravity profoundly alters leukocyte number and distribution in a mammalian model and that some aberrations persisted throughout the three weeks of the study. In certain cases, the detected changes were similar to those observed after whole-body irradiation. In future investigations we hope to combine hypergravity with low-dose rate irradiation and immune challenge.     

Binding specificity of siglec7 to disialogangliosides of renal cell carcinoma: possible role of disialogangliosides in tumor progression

The G protein beta3 subunit (GNB3) 825T allele is predictive of enhanced Gi protein activation. Studying the influence of C825T allele status on cellular in vitro immune responses towards recall antigens and interleukin-2 stimulation we observed a 2-4-fold, significantly increased proliferation in homozygous 825T (TT) vs. C825 allele (CC) carriers. Furthermore, lymphocyte chemotaxis and CD4(+) T cell counts of individuals with TT+TC genotypes were significantly enhanced compared to the CC genotype. In summary, it appears that C825T allele status is highly predictive of immunocompetence and could be a candidate gene in disorders associated with inadequate immune response.     

Effects of retinoic acid on the human lymphocyte response to mitogens

Nontoxic concentrations of retinoic acid enhance DNA synthesis of human peripheral blood lymphocytes in response to phytohemagglutinin or rabbit-antihuman thymocyte globulin, whereas the response to concanavalin A or pokeweed mitogen remained unaffected. Retinoic acid-induced stimulation of lymphocyte reactivity to phytohemagglutinin or antithymocyte globulin was most evident in T cell-enriched subpopulations and required the near-concurrent addition of retinoic acid and mitogens. Retinoic acid-mediated enhancement of lymphocyte proliferation in response to phytohemagglutinin or antithymocyte globulin was paralleled by a concomitant suppression of immune interferon production of lymphocytes stimulated with these mitogens. These findings allow further studies on the immunoregulatory action of retinoids in vitro.     

Lymphocyte subpopulations and cytokine production in paracoccidioidomycosis patients.

Despite the postulated role of the immune system in the control of the infection by Paracoccidioides brasiliensis, only a few studies have addressed this point in patients. The determination of total lymphocytes and their subpopulations in 6 untreated patients with the chronic form of paracoccidiodomycosis showed that half of them were lymphopenic, because of low number of CD4+ T-lymphocytes. All patients had low CD4/CD8 ratios. On the contrary, B-lymphocytes were normal in all patients. An additional patient, studied on treatment with ketoconazole, had normal lymphocyte counts in all subpopulations, as did one of the patients previously studied at diagnosis when he received specific antimycotic treatment. The production of interferon and tumor necrosis factor, determined by bioassay in supernatants of mononuclear blood cells of the patients, induced by interleukin 2 in vitro was significantly lower than that of normal subjects. These results show that patients with paracoccidioidomycosis have a defect in blood lymphocyte subsets as well as in the ability to produce regulatory cytokines.     

高原低氧免疫损伤及其干预措施的研究

目的:探讨高原低氧损伤免疫系统的特征及其可能机制,研究高原低氧免疫损伤的干预措施。方法:测定低氧暴露不同时间小鼠免疫器官指数、外周血和免疫器官T淋巴细胞亚群的变化;观察小鼠免疫器官淋巴细胞凋亡率及小鼠肺脏和肾脏病理学改变。采用预防给药方式,研究中药组方对低氧免疫损伤小鼠的干预作用。结果:①模拟海拔8000m低氧暴露8h后,小鼠胸腺CD4+CD8+细胞数显著下降,CD4+CD8-、CD4-CD8+细胞数显著增加(P0.01);低氧暴露3d后,外周血CD4+细胞明显减少(P0.05),CD4+/CD8+比值显著降低(P0.05),胸腺CD4+CD8+细胞数进一步下降,CD4+CD8-、CD4-CD8+细胞数进一步增加,小鼠脾脏、胸腺淋巴细胞晚期凋亡和坏死率均显著增加(P0.05);低氧暴露6d后,小鼠脾指数显著性增加(P0.01);胸腺指数显著性降低(P0.01),脾CD4+、CD8+细胞数显著降低(P0.01),脾脏和胸腺淋巴细胞晚期凋亡率和坏死率进一步增加(P0.01),活细胞率显著降低(P0.01),脾脏淋巴细胞早期凋亡率显著增加(P0.01)。整个低氧暴露过程中外周血CD8+无显著性变化。②新复方党参、香杞多糖、二者联合应用均能显著增加低氧免疫损伤小鼠外周血CD3+、CD4+、脾脏CD4+的细胞水平(P0.01,P0.05),对脾脏CD8+细胞水平没有显著影响。香杞多糖及其与新复方党参联合应用均能进一步降低胸腺CD4+CD8+,进一步增加CD4+CD8-的细胞水平(P0.01),未见对CD4-CD8+细胞水平的影响;新复方党参对低氧免疫损伤小鼠胸腺没有显著性影响。结论:模拟海拔8000m低氧暴露后小鼠外周发挥免疫作用的淋巴细胞数减少可能与低氧暴露早期淋巴细胞凋亡率和坏死率增加和肺脏淋巴细胞分布增多有关。新复方党参和香杞多糖作为低氧免疫损伤干预措施,具有一定发展前景。     

Circadian rhythms in surface molecules of rat blood lymphocytes

The present article examines whether the expression of certain surface molecules that trigger immune responses shows a circadian rhythm. We also analyzed the rhythms in the number and percentage of lymphocyte subpopulations, in the leukocyte differential counts, and in the total red and white blood cell counts. Blood samples obtained from rats at 2-h intervals for 24 h were stained with several mouse monoclonal antibodies directed against lymphocyte surface molecules and processed by flow cytometry. The number of B, total T, Tgammadelta, Th, and Ts/c cells followed a 24-h rhythm with a peak in the first half of the resting period. The expression of CD45, CD5, CD3, and CD4 followed a circadian rhythm. Their acrophases suggested temporal association between CD45 and CD5 at the end of the active phase and between CD4 and CD3 at the beginning of this phase. This temporal organization could have an important role for immune cell function.     

Verotoxin 1 from Escherichia coli affects Gb3/CD77+ bovine lymphocytes independent of interleukin-2, tumor necrosis factor-alpha,and interferon-alpha

Verotoxin (VT)-induced immunomodulation has been implicated in the ability of VT-producing Escherichia coli (VTEC) to cause persistent infections in cattle. VT1, also referred to as Shiga toxin 1, is a potent cytotoxin that modulates cytokine secretions and functions. This prompted the current investigation to examine whether the inhibiting effect of VT1 on bovine lymphocytes correlates with the expression of the cellular VT1 receptor Gb3/CD77 or is mediated instead via perturbation of cytokine secretion. Using blood mononuclear cells stimulated by mitogens as a model, VT1 significantly blocked lymphoblast transformation and proliferation in the BoCD8+ T cell and BoCD21+ B cell population. In contrast, VT1 dramatically reduced the number of viable Gb3/CD77+ blast cells within all subpopulations identified (BoCD2+, BoCD4+, BoCD8+, WC1+ [i.e., gammadelta T cells] BoCD21+, and BoCD25+). Similar effects of VT1 were observed when the culture medium was supplemented with selected cytokines: tumor necrosis factor-alpha-sensitizing endothelial cells against VT1, interferon-alpha (IFN-alpha) as bovine IFN-alpha receptors are partially homologous to the B-subunit of VT1, and interleukin-2 that is critical for lymphocyte proliferation in vitro. The addition of these cytokines was neither able to mimic nor to overcome the effects of VT1. Therefore, it is concluded that VT1 directly acts on bovine lymphocytes rather than inducing a cytokine-mediated effect. VT1 considerably affects all main bovine lymphocyte subpopulations, implicating that the immune system is a predominant target for VT1 in cattle.     

Statin treatment increases formation of carbon monoxide and bilirubin in mice: a novel mechanism of in vivo antioxidant protection

Heme oxygenase (HO) has a central role in cellular antioxidant defences and vascular protection, and it may mediate pleiotropic actions of drugs used in cardiovascular therapy. We investigated whether long-term use of statins upregulates HO activity and increases carbon monoxide (CO) and bilirubin levels in vivo. Adult FvB mice were given atorvastatin or rosuvastatin (5 mg/kg) daily by i.p. injections for 1, 2, or 3 weeks. HO activity, tissue CO, bilirubin, and antioxidant levels, total plasma bilirubin, and carboxyhemoglobin (COHb) were measured. Fold changes in heart HO activity significantly increased after 1, 2, and 3 weeks of atorvastatin (1.24 +/- 0.06 (p < or = 0.05); 1.29 +/- 0.26 (p < or = 0.03); 1.33 +/- 0.08 (p < 0.01), respectively) and 2 and 3 weeks of rosuvastatin (1.23 +/- 0.20 (p < or = 0.03); 1.63 +/- 0.42 (p < 0.01), respectively). Heart tissue CO and COHb levels also increased after 3 weeks with atorvastatin (1.30 +/- 0.24 (p < or = 0.05); 1.92 +/- 0.17 (p < or = 0.001), respectively) and rosuvastatin (1.47 +/- 0.13 (p < or = 0.004); 1.63 +/- 0.12 (p < or = 0.001), respectively). Significant increases in heart antioxidant levels were observed after statin treatment and corroborated by heart bilirubin content elevations. Antioxidant level increases were abolished by treatment with an HO inhibitor. These findings suggest that the induction of HO and the production of its products, CO and bilirubin, may be a mechanism by which statins exert antioxidant actions and confer cardioprotection in vivo.     

Prolonged statin administration does not act on the cell-mediated immunity of HIV-infected dyslipidemic patients treated with a steady and effective highly active antiretroviral therapy. A two-year prospective study of statin versus fibrate administration

OBJECTIVE: To assess whether statin administration for HIV-associated hyperlipidemia has long-term effects on immune recovery (as expressed by the trend of mean CD4+ lymphocyte count), in patients on a virologically-active HAART regimen since 12 months or more. METHODS: Single-centre, open-label, prospective study of 301 hyperlipidemic patients treated with statins (99 cases, with a predominant hypercholesterolemia), fibrates (116 subjects, when hypertriglyceridemia prevailed), or a isolated dietary/exercise program (86 patients, used as a control group). Neither epidemiological nor clinical, virological, or immunological differences were detected among the three study groups at baseline. During the subsequent follow-up, patients were excluded from evaluation should virological efficacy was not maintained, and/or initial hypolipidemic therapy was modified or interrupted for any reason. RESULTS: The quarterly assessment of mean CD4+ lymphocyte count did not disclose any statistically significant difference among the three study groups, since baseline and until at least 24 consecutive months of follow-up. Our data tend to exclude relevant in vivo negative activities of statins on immune system recovery of HIV-infected individuals who undergo a virologically effective HAART treatment. CONCLUSIONS: Multiple, pleiotropic features have been attributed to both statins and fibrates, and also apparently significant effects on laboratory markers of HIV disease progression have been recently claimed or expected. Despite some preliminary in vitro and ex-vivo models, both the main hypolipidemic classes administered for the management of HIV-related dyslipidemia (both statins and fibrates) do not seem to act significantly on clinical immune response of patients successfully treated with HAART. Multifactorial pathways are expected to interact with the cell-mediated immune system of HIV-infected patients undergoing successful HAART, and further studies are needed to elucidate whether more subtle immune effects might be prompted by a long-term administration of hypolipidemic drugs in this speciasl setting.     

Antigen-dependent and -independent mechanisms of T and B cell hyperactivation during chronic HIV-1 infection

Continuous loss of CD4(+) T lymphocytes and systemic immune activation are hallmarks of untreated chronic HIV-1 infection. Chronic immune activation during HIV-1 infection is characterized by increased expression of activation markers on T cells, elevated levels of proinflammatory cytokines, and B cell hyperactivation together with hypergammaglobulinemia. Importantly, hyperactivation of T cells is one of the best predictive markers for progression toward AIDS, and it is closely linked to CD4(+) T cell depletion and sustained viral replication. Aberrant activation of T cells is observed mainly for memory CD4(+) and CD8(+) T cells and is documented, in addition to increased expression of surface activation markers, by increased cell cycling and apoptosis. Notably, the majority of these activated T cells are neither HIV specific nor HIV infected, and the antigen specificities of hyperactivated T cells are largely unknown, as are the exact mechanisms driving their activation. B cells are also severely affected by HIV-1 infection, which is manifested by major changes in B cell subpopulations, B cell hyperactivation, and hypergammaglobulinemia. Similar to those of T cells, the mechanisms underlying this aberrant B cell activation remain largely unknown. In this review, we summarized current knowledge about proposed antigen-dependent and -independent mechanisms leading to lymphocyte hyperactivation in the context of HIV-1 infection.     

Cadmium exposure of rainbow trout, Salmo gairdneri Richardson: effects on immune functions

Differential leucocyte counts, phagocytosis, humoral antibody response and the in vitro blasto-genetic response to mitogens (lipopolysaccharide and Concanavalin A) and to an antigen ( Vibrio anguillarum ) were studied in rainbow trout exposed to 0,0.7 or 3.6 μg Cd 1⁻¹ for 12 weeks.
Although the fish did not exhibit any clinical or histological changes, cadmium exposure was found to affect two of the immune parameters measured. The cellular response of fish immunized with V. anguillarum to the homologous antigen was significantly lower for splenocytes obtained from fish exposed to cadmium for 9 weeks (3.6 μg Cd 1⁻¹ group) than for splenocytes obtained from non-exposed fish. Conversely, the humoral antibody response to V. anguillarum O-antigen was higher in the 3.6 μg Cd 1⁻¹ group than in the non-exposed group. Protective immunity of fish vaccinated against V. anguillarum was equally as good in the cadmium-exposed group as in the non-exposed group. No cadmium-induced changes in differential leucocyte counts or in the proportions of phagocytic cells were observed.     

Immunoregulatory properties of fractions from human pregnancy urine: evidence that human chorionic gonadotropin is not responsible.

The immunologically privileged position of the histoin-compatible fetus and placenta is a striking example of a physiologic immunoregulatory mechanism. This study was designed to examine the effects of human chorionic gonadotropin (HCG) on the recognitive proliferative phase and the cytotoxic effector phase of in vitro cell-mediated immune responsiveness, since HCG has previously been reported to be immunosuppressive in vitro and in vivo. Commercial preparations of HCG were found to be potent inhibitors of lymphocyte proliferative responses to nonspecific mitogens like phytohemagglutinin (PHA), specific antigens such as streptolysin-O (SLO), and allogeneic cells as measured in the one-way mixed leukocyte response. Cytotoxic effector function of lymphocytes as measured by antibody-dependent cellular cytotoxicity (ADCC) and mitogen-induced cellular cytotoxicity were also markedly inhibited by these preparations. However, the 50% inhibitory concentration varied widely from lot to lot of these commercial materials. After dialysis, a portion of the inhibitory activity was lost from some but not all HCG lots. The dialysate from those lots with diminished activity was found to be immunosuppressive in vitro but contained no HCG detectable by radioimmunoassay. Following dialysis, the immunosuppressive activity of the various HCG lots remained variable and correlated poorly with values for HCG obtained by a double antibody radioimmunoassay. HCG preparations purified to a homogeneity sufficient for amino acid sequence were found to be only minimally immunosuppressive to the in vitro PHA response and had almost no effect on proliferative responses to antigens and allogeneic cells. These data do not support the concept of a primary immunoregulatory role for HCG, but they suggest that other uncharacterized compounds partially co-purified from pregnant urine along with HCG may have such immunoregulatory activity. Further characterization and identification of this immunoregulatory material(s) is essential, since it appears to have many of the properties of an ideal immunosuppressive compound: a) nontoxicity, b) ready reversibility, c) activity at very low concentration, and d) activity on a broad range of cellular immune functions.