Cytokines as an adjuvant to tumor vaccines: Efficacy of local methods of delivery

Background: We examined alternative methods of delivering cytokines as an adjunct for priming lymph node (LN) cells draining sites of vaccine inoculation for the purpose of generating immune cells for adoptive immunotherapy. Methods: Using syngeneic murine tumors we examined the ability of IL-2, IL-4, or GM-CSF delivered locally to a site of tumor inoculum to induce antitumor reactive draining LN cells. Mice were inoculated subcutaneously with tumor cells transduced to secrete cytokine; tumor cells admixed with fibroblasts transduced to secrete cytokine; or intralesional inoculation of cytokine in established tumor to induce sensitized LN cells capable of mediating tumor regression in adoptive transfer. Results: Both IL-4 and GM-CSF cytokines were effective in enhancing the antitumor reactivity of vaccine-primed LN cells compared to IL-2, which was ineffective. The local delivery of GM-CSF by autocrine or paracrine secretion of genetically engineered cells, as well as direct intratumoral delivery was capable of upregulating LN sensitization compared to systemic administration, which did not. Conclusions: The local delivery of GM-CSF as an adjuvant for tumor vaccination can be accomplished by various methods, including direct injection, which avoids the need for gene transfer.     

乌苯美司体外对人单核细胞功能的活化作用

观察了国产乌苯美司（乌比美克）体外对人单核细胞功能的影响：①０．０１￣１００μｇ／ｍｌ乌苯美司能直接诱导人单核细胞生成ＩＬ－１；②经０．１μｇ／ｍｌ乌苯美司作用４ｈ后，人单核细胞即开始分泌ＩＬ－１，２４ｈ达到高峰，以后逐渐下降；③经１０￣１００μｇ／ｍｌ乌苯美司预处理，单核细胞可促进ＮＫ细胞活性，而经０．０１￣０．１μｇ／ｍｌ乌苯美司处理，单核细胞则抑制ＮＫ细胞活性。     

Pheophytin a, a low molecular weight compound found in the marine brown alga Sargassum fulvellum, promotes the differentiation of PC12 cells

We identified and characterized a neurodifferentiation compound from the marine brown alga Sargassum fulvellum collected from the Japanese coastline. Several instrumental analyses revealed the compound to be pheophytin a. Pheophytin a did not itself promote neurite outgrowth of PC12 cells. However, when PC12 cells were treated with a low concentration of pheophytin a (3.9 microg/ml) in the presence of a low level of nerve growth factor (10 ng/ml), the compound produced neurite outgrowth similar to that produced by a high level of nerve growth factor (50 ng/ml). Pheophytin a also enhanced signal transduction in the mitogen-activated protein kinase signaling pathway, which is also induced by nerve growth factor. The effect of pheophytin a on neurite outgrowth of PC12 cells was completely blocked by U0126, a representative mitogen-activated protein kinase kinase inhibitor. These results suggest that pheophytin a enhances the neurodifferentiation of PC12 cells in the presence of a low level of nerve growth factor and that this effect is mediated by activation of a mitogen-activated protein kinase signaling pathway.     

PHA对单产和联产白细胞介素-2活性的影响

本文研究了用人外周血白细胞在细胞浓度为5×10~5个/ml、培养时间为24h,PHA加量对单独生产白细胞介素_2(单产)及联合生产a_干扰素、白细胞介素-2(联产)的影响.单产中,以25μg/mlPHA刺激量为宜;联产中以100μg/ml刺激量最好.联产比单产所得白细胞介素-2产量高10倍以上,且纯度高.     

冠心病患者血清同型半胱氨酸与叶酸、维生素B12水平的变化

目的 探讨冠心病患者血清同型半胱氨酸(HCY)与叶酸、维生素B12浓度的变化及其相关性。方法 选择84例经冠状动脉造影术证实为冠心病的患者，应用荧光偏振免疫分析法(FPIA)测定血清HCY浓度，离子捕获免疫分析法(ICIA)测定血清叶酸浓度，非均相微粒子酶免疫分析法（MEIA)测定血清维生素B12浓度。结果 冠心病患者血清HCY浓度增高，与正常对照组比较有显著性意义(P＜0．001)，而叶酸、维生素B12浓度则降低，与正常对照组比较有显著性意义(P＜0．001)，以上两种变化呈负相关(P＜0．001)。结论 同型半胱氨酸血症是冠心病的新的独立危险因素，叶酸、维生素B12缺乏可能是诱发高HCY的重要因素。     

IL-12表达障碍与支气管哮喘关系研究进展

支气管哮喘是由Th2介导的Ⅰ型变态反应,与内源性IL-12生成不足有关,该文综述了IL-12的生物学效应、IL-12表达障碍与支气管哮喘的关系以及IL-12、重组IL-12（rIL-12）在支气管哮喘治疗方面的应用前景。IL-12与Ⅰ型变态反应关系密切,内源性IL-12表达不足使支气管哮喘患者免疫系统向Th2方向偏移,在过敏原或病毒等外因的刺激下发生支气管哮喘。用IL-12对支气管哮喘进行免疫治疗已在动物实验中取得了显著效果,将IL-12、rIL-12或IL-12的内源性诱生物应用于人体的方法也在不断探索中并取得了一定效果,基于IL-12的治疗方法可能为支气管哮喘等变应性疾病的免疫治疗开辟新的途径。     

脱水穿心莲内酯珀琥酸半酯单钾盐家兔体内药代动力学实验研究

采用紫外分光光度法测定脱水穿心莲内酯琥珀酸半酯单钾盐血药浓度,并对腹腔单剂量注射给药后家兔体内药代动力学进行了研究。用计算机对血药时间数据进行了曲线拟合。结果表明:该药腹腔注射给药在家兔体内的转运符合二室开模型动力学方程。     

Recombinant human IL-16 inhibits HIV-1 replication and protects against activation-induced cell death (AICD)

The chemoattractant cytokine IL-16 has been reported to suppress lymphocyte activation and to inhibit HIV-1 replication in acutely infected T cells. We have cloned and expressed human IL-16 in Escherichia coli and investigated whether the recombinant protein could regulate the level of lymphocyte apoptosis from HIV-1-infected subjects. After purification and refolding, only 2–10% of the recombinant cytokine was present in a biologically active homotetrameric form. This could explain the need for high concentrations of the bacterially derived IL-16 to induce significant inhibition of HIV-1 replication. Addition of IL-16 to unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-1-infected subjects did not modify the observed level of spontaneous lymphocyte apoptosis. In contrast, IL-16 added to PBMC cultures stimulated with anti-CD3, anti-CD95 or dexamethasone reduced significantly the percentage of lymphocytes undergoing AICD. This effect was found to correlate with the ability of the cytokine to decrease CD95 expression on activated CD4⁺ T cells. Comparative studies on PBMC from healthy individuals indicated that the regulation of apoptosis levels by IL-16 is a complex phenomenon and could depend on the nature of the activator used and/or the immune status of lymphocytes tested. The outcome of CD4 cross-linking on T cells by various ligands is discussed in the context of the observed beneficial activities of IL-16 and its potential role in the treatment of HIV disease.     

三七多糖对创伤大鼠CD+4/CD+8和IL-2水平的影响(摘要)

观察三七多糖对创伤大鼠免疫功能的影响.方法:40只SD大鼠,随机分为正常对照组(A)、创伤对照组(B)、创伤后三七多糖28.5 mg·kg-1.