病毒性肝炎和肝硬化患者IL－6、TNF－α的变化

为研究白细胞介素－６（ＩＬ－６）、肿瘤坏死因子（ＴＮＦ－α）在肝炎和肝硬化（ＬＣ）患者中的作用。检测了１５例正常人，１８例急性病毒性肝炎（ＡＨ），３７例慢性肝炎（ＣＨ），２０例ＬＣ患者血清及外周血单个核细胞（ＰＢＭＣ）的ＩＬ－６、ＴＮＦ－α水平。结果以ＣＨ患者ＩＬ－６、ＴＮＦ－α水平最高（血清及ＰＢＭＣ的ＩＬ－６水平分别为７２．１±３２．９４Ｕ／ｍｌ，１４０．７±３３．５Ｕ／ｍｌ；血清及ＰＢＭＣ的ＴＮＦ－α水平为３．９７±１．３８ｎｇ／ｍｌ，６．３５±１．４１ｎｇ／ｍｌ）。恢复期或稳定期ＴＮＦ－α和ＩＬ－６水平明显低于急性期或活动期（Ｐ＜０．０１）。ＣＨ患者肝组织学活动指数（ＨＡＩ）分数与ＰＢＭＣＩＬ－６和ＴＮＦ－α水平呈正相关（γ分别为０．８９，０．６８；Ｐ＜０．０５）。提示ＩＬ－６和ＴＮＦ－α是肝脏损害重要的炎症介质，介导肝细胞损害。     

慢性重型肝炎患者外周血单个核细胞内干扰素和白细胞介素的表达及意义

目的探讨慢性重型肝炎（ＣＳＨ）病人外用血单个核细胞（ＰＢＭＣ）内干扰素－γ（ＩＦＮ－γ）及白细胞介素－４（ＩＬ－４）的表达及其临床意义。方法常规分离ＰＢＭＣ,在ＰＭＡ、Ｉｏｎｏｍｙｃｉｎ、Ｍｏｎｅｎｓｉｎ的刺激下,采用流式细胞术（ＦＡＣＳ）,对１７例ＣＳＨ患者及１９例正常健康者ＣＤ４＋Ｔ细胞内ＩＦＮ－γ和ＩＬ－４的表达进行分析,并应用荧光定量聚合酶链反应检测ＨＢＶ ＤＮＡ含量。结果 ＣＤ４＋Ｔｈ１、 Ｔｈ２细胞在ＣＳＨ组分别为７．２％—２６．３％（平均１５％）和０、ｌ％—１０．９％（平均２．０％）,正常对照组则分别为２．２％—１１．９％（平均５．９％）和０．４％—３．９％（平均２．２％）;ＣＤ４＋Ｔｈ１细胞百分数两组间差异有显著意义（Ｐ＜０．０１）。荧光定量ＰＣＲ结果表明ＣＳＨ组中１３例ＨＢＶ　ＤＮＡ阳性,其ＨＢＶ ＤＮＡ的含量与ＩＦＮ－γ表达细胞百分数呈负相关。结论 Ｔｈ１细胞与肝脏的炎症活动明显相关,ＩＦＮ－γ的表达对ＨＢＶ复制可能具有一定的影响。     

病毒性肝炎患者血清HGF和TGF—β1水平的临床意义

目的：探讨血清肝细胞生长因子（ｓＨＧＦ）和转化生长因子－β＿１（ＴＧＦ－β１）水平在病毒性肝炎患者中的临床意义。方法：选１３９例病毒性肝炎患者，以双抗体夹心ＥＬＩＳＡ检测ｓＨＧＦ，以改良ＭＶ１ＬＵ细胞生长抑制ＭＴＴ法检测ＴＧＦ－β＿１活性，同时检测其肝功能、肝纤维化、甲胎蛋白等指标。结果：各型病毒性肝炎患者ｓＨＧＦ水平及ＴＧＦ－β＿１活性均明显高于正常人水平（Ｐ值均＜０．０１）。ＴＧＦ－β１活性增高以肝硬化和重症肝炎最为显著（分别为９．４４±２．１７ｎｇ／ｍｌ和８．４２±２．５４ｎｇ／ｍｌ）。ｓＨＧＦ水平与ＴＧＦ－β＿１活性相关（Ｐ值＜０．０１）。结论：ｓＨＧＦ水平能反映患者肝细胞损伤及肝功能障碍程度，并与肝纤维化程度也可能有关。     

肾综合征出血热患者血清IL-6、尿液肿瘤坏死因子、IL-6、IL-8的检测

目的探讨细胞因子在肾综合征出血热（ＨＦＲＳ）发病中的作用。方法采用双抗体夹心ＥＬＩＳＡ法对４８例ＨＦＲＳ患者及２０例正常人血清白细胞介素（ＩＬ）－６、尿液肿瘤坏死因子（ＴＮＦ）、ＩＬ－６、ＩＬ－８进行动态检测。结果ＨＦＲＳ患者血清ＩＬ－６、尿液ＴＮＦ、ＩＬ－６、ＩＬ－８含量较对照组明显增高（Ｐ＜０．００１）；发热期已增高，低血压期继续增高，少尿期达峰值；其含量随病情加重而升高，各型间差异有显著性；血清ＩＬ－６与特异性抗体升高有明显关系，与血清β２－微球蛋白（β２－ＭＧ）、血尿素氮（ＢＵＮ）、血肌酐（Ｃｒ）均呈高度正相关；尿液ＩＬ－６与ＴＮＦ、ＩＬ－８呈显著正相关（ｒ＝０．５６２１，Ｐ＜０．００５；ｒ＝０．３８４５，Ｐ＜０．０１）。结论ＨＦＲＳ患者病程中ＴＮＦ、ＩＬ－６、ＩＬ－８均处于高活性状态，ＩＬ－６与体液免疫反应亢进所致的免疫病理损伤有关，ＩＬ－６、ＩＬ－８、ＴＮＦ参与肾脏的免疫损伤，可作为判定患者预后和转归的指标。     

老年心衰患者血清sIL—2R及T细胞亚群的变化

目的研究老年心衰（ＨＦ）患者血清中可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）及Ｔ淋巴细胞亚群（Ｔ－ＬＳ）的变化及临床意义。方法血清ｓＩＬ－２Ｒ测定采用酶联免疫吸附双抗体夹心法，Ｔ－ＬＳ采用抗体致敏的红细胞花环法。检测４０例老年ＨＦ及３０例正常组血清ｓＩＬ－２Ｒ及Ｔ－ＬＳ的变化。结果老年ＨＦ患者血清ｓＩＬ－２Ｒ水平与正常组比较显著增高（Ｐ＜０．０５，Ｐ＜０．０１）；Ｔ－ＬＳ在老年ＨＦ与正常组比较显著下降（Ｐ＜０．０５，Ｐ＜０．０１）。结论血清ｓＩＬ－２Ｒ水平及细胞免疫低下可影响老年ＨＦ的发病及预后     

GM—CSF及IL—4增强肝癌患者树突状细胞免疫功能

目的　探讨粒／ 巨噬细胞集落刺激因子（ ＧＭＣＳＦ） 及白介素４（ＩＬ４） 对正常成人及肝癌患者树突状细胞（ＤＣ） 表面人白细胞抗原（ＨＬＡ）ＤＲ 及Ｂ７２ 等免疫分子表达及其免疫功能的影响。方法　以ＧＭＣＳＦ 及ＩＬ４ 联合刺激正常成人（ｎ ＝ １０） 及肝癌患者（ｎ ＝ １０）ＤＣ,检测经ＧＭＣＳＦ 及ＩＬ４ 联合刺激前后ＤＣ 表面ＨＬＡＤＲ 及Ｂ７２ 表达水平及ＤＣ 免疫功能变化。结果　经ＧＭＣＳＦ 及ＩＬ４ 联合刺激后ＤＣ 表面ＨＬＡＤＲ 及Ｂ７２ 表达水平在肿瘤患者（６－７ ±１－６ 、６－１ ±１－１ 增至１３－１ ±２－３ 、１１－４ ±２－０ＶＯＦ,Ｐ＜ ０－０１） 及正常成人（１０－７ ±１－４ 、９－６ ±１－２ 增至１４ ±２－２ 、１１ ±１－７ＶＯＦ,Ｐ＜ ０－０５） 均有增高;该ＤＣ 免疫诱导能力亦相应增强（ 肝癌患者：由３１００ ±１２０ 增至６４００ ±１４０ｃｐｍ ,Ｐ＜ ０－０１ ;正常人：由６２００ ±９０ 增至７０００ ±１１０ｃｐｍ ,Ｐ＞ ０－０５） 。结论　ＧＭＣＳＦ 及ＩＬ４ 联合刺激能增强正常成人及肝癌患者ＤＣ 表面ＨＬＡＤＲ 及Ｂ７２ 表达水平并进一步增强ＤＣ 免疫功能。提示联合应     

rhIL—6,rhGM—CSF和rhEPO对人造血干细胞的作用

重组人白细胞介素 ６和重组人粒－单细胞集落刺激因子与正常人造血干细胞培养１周后，ＩＬ－６组细胞数增至４．３±０．６倍，ＧＭ－ＣＳＦ组细胞数增至９．４±０．９倍；ＩＬ－６＋ＧＭ－ＣＳＦ组细胞数增至１３．７±１．０倍，明显高于对照组（Ｐ＜０．０１）。红系集落生成单位集落分析：ＩＬ－６单独应用未见ＣＦＵ－Ｅ集落形成，仅有粒－单细胞集落生成单位集落形成；ＩＬ－６＋促红细胞生成素且则ＣＦＵ－Ｅ集落数明显高于     

巨噬细胞集落刺激因子（M—CSF）抑制c—kit的表达

已经证实细胞原癌基因ｃ－ｋｉｔ的蛋白产物是造血干细胞因子（ＳＣＦ）或肥大细胞生长因子（ＭＧＦ）的细胞膜上受体，对于造血细胞增殖和分化调节起重要作用，ｃ－ｋｉｔ的表达受到多种细胞因子的调节，其中已知ＩＬ－４，和ＴＧＦ－β可抑制它的表达，所来许多实验都发同ＳＣＦ与ＩＬ－３，ＧＭ－ＣＳＦ，Ｇ－ＣＳＦ，ＥＰＯ，ＩＬ－１和ＩＬ－６对造血有协同增强作用，但是Ｍ－ＣＳＦ无协同作用，Ｍ－ＣＳＦ的受体是原癌基因ｃ－     

胸腺肽α1治疗重症肝炎的免疫调节研究

为了解日达仙的免疫调节作用,选取１８例下肝炎病人用日达仙（Ｔα１）治疗,并在治疗前后检测内毒素（ＬＳＰ）、肝瘤坏死因子（ＴＮＦ）、白细胞介素２受体（ＩＬ－２Ｒ）、白细胞介素４（ＩＬ－４）、白细胞介素６（ＩＬ－６）、及Ｔ细胞亚群（ＣＤ８＾＋、ＣＤ４＾＋）。结果治疗前ＬＳＰ、ＴＮＦ、ＩＬ－２Ｒ、ＩＬ－６、ＣＤ８＾＋均增高９Ｐ〈０．０１）,而ＩＬ－４及ＣＤ４＾＋降低。经Ｔα１治疗后ＬＳＰ、ＴＦ、ＩＬ－２     

病毒性肝炎患者血清转化生长因子—β1活性及其与肝纤维化的关系

为了探讨转化生长因子－β（ＴＧＦ－β１）在肝纤维化发病机制中的作用，采用ＭＶ１ＬＵ细胞了制ＭＴ法，检测了１０８例病毒性肝炎患者血清ＴＧＦ－β１活性，同时用放免法检测血清前季Ⅲ型胶原（ＰＣⅢ）、透明质酸（ＨＡ）层粘蛋白（ＬＮ）的含量，结果表明各型肝炎患者ＴＧＦ－β１活性较正常对照都明显增高（Ｐ〈０．０１）。随病情的发展，ＴＧＦ－β１活性逐渐增高，ＰＣⅢ、ＨＡ、ＬＮ含量也明显增加，各组间差异均有显著性     

Regulation of sodium iodide symporter gene expression in FRTL-5 rat thyroid cells.

The sodium iodide symporter (NIS), first identified in FRTL-5 cells, plays a critical role in iodide transport in the thyroid gland and in the production of the iodine-containing thyroid hormones. The aim of our study was to examine the regulation of NIS RNA steady-state levels and protein expression as well as functional activity in FRTL-5 cells. FRTL-5 cells cycling in media containing thyrotropin (TSH) were incubated for 48 hours with dexamethasone (10(-8)-10(-5) M), triiodothyronine (T3; 10(-9)-10(-6) M), methimazole (100 microM), propylthiouracil (PTU; 100 microM), perchlorate (10 microM) and potassium iodide (40 microM). In other experiments, cells were treated for 48 hours with various cytokines including interleukin-6 (IL-6) (100 U/mL), interferon-gamma (IFN-gamma) (100 U/mL), tumor necrosis factor-alpha (TNF-alpha) (10 ng/ml), IL-1alpha (100 U/mL), and IL-1beta (100 U/mL). Northern blot analysis using a 32P-labeled rat NIS-specific cDNA probe (nucleotides 1397-1937) revealed NIS mRNA as a single species of approximately 3 kb. When normalized for beta-actin mRNA signal intensities, NIS RNA steady-state levels in viable FRTL-5 cells were suppressed by approximately 80% after incubation with dexamethasone and T3 in a concentration-dependent manner. Iodide accumulation was decreased by up to 40% after incubation with dexamethasone and T3, respectively, in a concentration-dependent manner. Using a rabbit polyclonal rNIS-specific antibody, Western blot analysis of FRTL-5 cell membranes revealed a 60% and 70% suppression of NIS protein expression after treatment with T3 (0.1 microM) and dexamethasone (1 microM), respectively. In additon, NIS RNA steady-state levels were decreased by approximately 50% after treatment of monolayers with methimazole, PTU, and potassium iodide, respectively. Incubation with methimazole and PTU resulted in a 20% and 25% decrease of iodide accumulation, respectively, whereas potassium iodide suppressed iodide accumulation by approximately 50%. Treatment of FRTL-5 cells with IL-6 and IL-1beta resulted in a 30% decrease of NIS RNA steady-state levels. IL-6 did not alter NIS functional activity, but IL-1beta suppressed iodide accumulation by approximately 25%. IFN-gamma and perchlorate failed to alter NIS RNA steady-state levels. In contrast to IFN-gamma that had no effect on iodide accumulation, perchlorate almost completely suppressed iodide accumulation. TNF-alpha and IL-1alpha failed to alter NIS RNA steady-state levels in higher passage numbers of FRTL-5 cells, whereas treatment with TNF-alpha and IL-1alpha of early passages of FRTL-5 cells (<20 cell passages) resulted in a 70% and 40% decrease of NIS RNA steady-state levels, respectively, and in a 20% suppression of NIS functional activity. In conclusion, our data suggest that various agents known to affect iodide transport are capable of differentially altering NIS gene expression and function in cultured thyroid cells. Suppression of NIS gene expression and function by certain cytokines may be responsible, at least in part, for the impaired radioiodine uptake by thyroid tissue in certain forms of thyroiditis.     

Soluble interleukin-2 receptor, interleukin-6 and interleukin-1 beta in patients with Crohn's disease and ulcerative colitis: preoperative levels and postoperative changes of serum concentrations.

Crohn's disease (CD) and ulcerative colitis (UC) show an intestinal activation of T cells and macrophages within the inflamed lesions. The aim of the present prospective study was to determine whether circulating interleukins (IL) represent useful markers of immune activation in vivo and to characterize their respective roles in monitoring disease activity. Serum concentrations of the soluble IL-2 receptor (sIL-2R), IL-6 and IL-1 beta were measured in 10 patients with CD and 10 patients with UC before, at day 10 and 2 years after resection of inflamed bowel segments. The data were correlated with neopterin, C-reactive protein and other standard parameters of disease activity. Preoperatively, mean sIL-2R concentration was 495 +/- 62 U/ml (mean +/- SEM; healthy controls; 210 +/- 25 U/ml; p less than 0.02) in CD and 705 +/- 120 U/ml (p less than 0.00002) in UC. The corresponding IL-6 serum concentrations were 37 +/- 6 U/ml in CD (controls: 11 +/- 0.6 U/ml; p less than 0.0036) and 33 +/- 6 U/ml (p less than 0.04) in UC. Two years postoperatively, sIL-2R was still elevated in 6 out of 9 patients in both disease groups. These patients did not differ from the remaining group with respect to disease activity. Serum IL-6, elevated in 7 patients with CD and in 6 patients with UC at day 10 postoperatively, had returned to normal in all patients by this time.(ABSTRACT TRUNCATED AT 250 WORDS)     

过氧化氢上调白细胞介素1β诱导人肺上皮细胞表达环氧合酶2

目的探讨过氧化氢(H2O2)对白细胞介素1β(IL-1β)诱导人肺上皮细胞(HPEC)环氧合酶2(COX-2)表达的影响.方法应用逆转录-聚合酶链反应(RT-PCR)半定量法和酶联免疫吸附试验 (ELISA)测定IL-1β、H2O2或二者联合干预后HPEC COX-2 mRNA表达量及前列腺素E2(PGE2)释放量的变化, 以不加任何试剂的细胞为对照组.结果 (1)COX-2 mRNA表达量1、5、10 mg/L 的IL-1β处理组COX-2 mRNA表达量分别为(143.1±7.2)%、(179.9±9.0)%、(190.0±9.5)%,对照组为(32.9±1.7)%,1、5、10 mg/L 的IL-1β处理组与对照组比较差异有显著性(P均<0.05); (2)培养基上清液PGE2浓度5、10 mg/L 的IL-1β处理组培养基上清液PGE2浓度分别为 (20.86±5.23)×10-6 g/L、(31.16±2.64)×10-6 g/L,对照组为(10.49±0.36)×10-6 g/L, 5、10 mg/L 的IL-1β处理组与对照组比较差异有显著性(P<0.05);(3) COX-2 mRNA表达量 0.10、0.25、0.50 mmol/L 的H2O2和IL-1β共处理组COX-2 mRNA表达量分别为 (149.2±7.5)%、(189.6±9.5)%、(239.1±12.0)%, IL-1β单独处理组为(66.1±3.7)%, 对照组为(41.6±2.1)%, 0.10、0.25、0.50 mmol/L 的H2O2和IL-1β共处理组与IL-1β单独处理组比较,差异有显著性 (P<0.05); (4)培养基上清液PGE2浓度0.10、0.25、0.50 mmol/L的H2O2和IL-1β共处理组,培养基上清液PGE2浓度分别为 (27.01±5.16)×10-6 g/L、(32.79±3.01)×10-6 g/L、(41.13±3.41)×10-6 g/L,对照组为(10.49±0.36)×10-6 g/L,0.10、0.25、0.50 mmol/L的H2O2和IL-1β共处理组与对照组比较差异有显著性(P<0.05).0.25、0.50 mmol/L的 H2O2和IL-1β共处理组PGE2浓度均与IL-1β单独处理组[(20.86±5.23)×10-6 g/L]比较差异有显著性 (P<0.05). 结论过氧化氢上调IL-1β对HPEC COX-2的诱导表达,其调节机制可能发生在转录水平.     

肿瘤坏死因子α、白细胞介素1β对牛肺动脉内皮细胞凋亡的影响及意义

目的　研究肿瘤坏死因子α(TNF α)、白细胞介素 1β(IL 1β)对牛肺动脉内皮细胞 (BPEC)损伤的机制及在急性肺损伤 (ALI)发病过程中的作用。方法　建立BPEC的体外培养 ,采用流式细胞仪膜联蛋白V 异硫氰酸荧光素 (Annexin VFITC)、碘化吡啶 (PI)染色检测TNF α、IL 1β对BPEC凋亡的影响以及抗TNF α单克隆抗体、AC DEVD CHO (caspase 3的竞争性抑制剂 )的保护效应。结果　 (1)TNF α作用 2 4h ,随着其浓度的增加 (浓度为 50 0、10 0 0、2 0 0 0U/ml) ,BPEC凋亡率逐渐增加 [分别为(8 2 1± 0 70 ) %、(9 63± 0 71) %、(17 43± 1 99) % ] ,与对照组 [(3 0 9± 0 0 8) % ]比较差异有显著性(P均 <0 0 5) ;(2 )TNF α (2 0 0 0U/ml)培养时间延长 (分别为 6、12、2 4、3 6h) ,BPEC凋亡率逐渐增加 [分别为 (6 72± 0 3 8) %、(7 72± 1 66) %、(12 95± 0 3 2 ) %、(17 70± 1 79) % ,P均 <0 0 5] ;(3 )加入抗TNF α单抗、AC DEVD CHO的TNF α组的BPEC凋亡率 [(7 78± 0 2 1) %、(7 3 2± 0 11) % ]显著高于单纯TNF α(2 0 0 0U/ml)组 [(10 59± 0 49) % ,P均 <0 0 1] ,而加入IL 1β的TNF α组的凋亡率 [(10 73±0 60 ) % ]与单纯TNF α组比较差异无显著性 (P >0 0 5)。结论　ALI过程中是TNF     

Long-term effects of thyroid stimulating hormone and insulin on intracellular pH in FRTL-5 cells.

We have studied the chronic effects of TSH (100 microU/ml) and insulin (10 micrograms/ml) on intracellular pH (pH(i)) in FRTL-5 cells using the pH sensitive probe 2'7-bis (2-carboxyethyl-5'-6') carboxyfluorescein. FRTL-5 cells were cultured on Petri dishes either in the presence of 4H, ie. Coons F-12 containing cortisol (10 nM), transferrin (0.5 microgram/ml), glycyl-histidyl lysine acetate (10 ng/ml) and somatostatin (10 micrograms/ml), or with 4H + insulin (5H), 4H + TSH, or 4H + TSH + insulin (6H). pH(i) was measured in small groups of cells by microspectrofluorimetry both in the presence and absence of bicarbonate ions after cells had been deprived of serum for at least a day. In the absence of TSH, insulin and bicarbonate ions, pH(i) was 7.26 +/- 0.18 (mean +/- SD, n = 49) rising to 7.89 +/- 0.09 (n = 59) and 7.43 +/- 0.1 (n = 55) in the presence of TSH (4H + TSH) and insulin (5H) respectively. Addition of both insulin and TSH (6H) resulted in a pH(i) of 7.75 +/- 0.09 (n = 40). In the absence of TSH and insulin, but the presence of bicarbonate ions, pH(i) was 7.29 +/- 0.12 (mean +/- SD n = 47) rising to 7.72 +/- 0.07 (n = 59) in 4H + TSH and 7.48 +/- 0.08 (n = 60) in 5H. pH(i) in the presence of both TSH and insulin was 7.81 +/- 0.03 (n = 60). In conclusion, both insulin and TSH caused an intracellular alkalinization, TSH markedly so, even in the presence of bicarbonate ions.     

Interferon-gamma and interleukin-4 differentially regulate ICAM-1 and VCAM-1 expression on human lung fibroblasts.

The expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and more specifically vascular adhesion molecule-1 (VCAM-1) on lung fibroblasts may be important for migration of inflammatory cells through the submucosa to the airway lumen in the asthmatic inflammatory response. This study aimed to assess which cytokines are regulating ICAM-1 and VCAM-1 expression on human lung fibroblasts. For this purpose, confluent fibroblast cultures (derived from lung tissue from a nonasthmatic donor) were stimulated for 4 h with interleukin (IL)-1beta, tumour necrosis factor (TNF)alpha, interferon (IFN)gamma, IL-4, IL-5 or transforming growth factor (TGF)beta. IL-1beta (optimal concentration (OC) 1 U x mL(-1)) and TNFalpha (OC 100 U x mL(-1)) both increased ICAM-1 and VCAM-1 expression. IFNgamma (OC 2 U x mL(-1)) increased only ICAM-1 expression and IL-4 (OC 5 ng x mL(-1)) increased only VCAM-1 expression, whereas IL-5 (20 ng x mL(-1)) and TGFbeta (10 ng x mL(-1)) did not influence ICAM-1 or VCAM-1 expression. ICAM-1 expression reached a plateau at 8-12 h after cytokine stimulation and remained constant for at least 24 h. VCAM-1 showed a transient increased expression within 24 h after IL-1beta and TNFalpha stimulation. In contrast, VCAM-1 expression did not decrease after maximal expression at 4 h upon IL-4 stimulation. It is concluded that the Helper-1T-cell, type cytokine interferon gamma and the Helper-2 T-cell type cytokine interleukin-4 differentially regulate intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on human lung fibroblasts. The proinflammatory cytokines interleukin-1beta and tumour necrosis factor alpha increase both intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, without differential regulation of the expression of these adhesion molecules.     

Production of various cytokines by normal human osteoblast-like cells in response to interleukin-1 beta and tumor necrosis factor-alpha: lack of regulation by 17 beta-estradiol.

We investigated, in five cell strains per experiment, whether several cytokines known or believed to have effects on bone resorption were produced by nearly homogeneous strains of cultured normal human osteoblast-like (hOB) cells that display virtually the complete phenotype of the mature osteoblast. In unstimulated hOB cells, we detected constitutive production of interleukin-6 (IL-6) (mean +/- SE, 122 +/- 32 pg/ml) and IL-8 (135 +/- 39 pg/ml), but not of IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), or tumor necrosis factor-alpha (TNF alpha). IL-1 beta in doses from 1-100 U/ml stimulated dose-dependent increases in IL-6 (r = 0.87; P less than 0.001) and IL-8 (r = 0.95; P less than 0.001). Similar increases occurred after stimulation with TNF alpha in doses from 3-300 U/ml. IL-1 beta and TNF alpha also stimulated GM-CSF production, but only at higher doses. 17 beta-Estradiol (10(-8) M) had no significant effect on the secretion of any of these cytokines, either constitutively or after stimulation with IL-1 beta or TNF alpha. Stimulated production of IL-4 was not detected after treatment with IL-1 beta or TNF alpha, and that of TNF alpha was not detected after treatment with IL-1 beta. We conclude that IL-6, IL-8, and GM-CSF, but not IL-4 and TNF alpha, are produced by highly differentiated normal human cells of the osteoblast lineage, but their secretion is not regulated by estrogen. However, we cannot exclude the possibility that estrogen regulation of these cytokines may occur during early stages of osteoblast differentiation.     

Nicotinamide partially reverses the interleukin-1 beta inhibition of glucose-induced insulin release in pancreatic islets.

Interleukin-1 beta (IL-1 beta) is known to inhibit glucose-induced insulin release by pancreatic islets. We studied the effect of nicotinamide, an inhibitor of poly[adenosine diphosphate (ADP)-ribose] synthetase and a free-radical scavenger, on this IL-1 beta-induced inhibition using rat pancreatic islets. In static experiments, groups of five islets were incubated for 24 hours in culture medium CMRL-1066, with or without 50 U/mL IL-1 beta, in the presence or absence of nicotinamide (dose range, 0 to 50 mmol/L), and then exposed for 1 hour to either 1.4 or 19.4 mmol/L glucose, 10 mmol/L arginine, or 10 mumols/L glyburide. Basal insulin secretion was 183 +/- 32 pg/islet/h (mean +/- SE, n = 7) and 176 +/- 39 (n = 7) in control islets and in islets exposed to 50 U/mL IL-1 beta, respectively. Glucose-stimulated insulin secretion was significantly reduced (185 +/- 41) in IL-1 beta-exposed islets in comparison to control islets (2,037 +/- 363). In parallel, arginine-stimulated insulin release was inhibited by IL-1 beta exposure (166 +/- 31 pg/islet/h, mean +/- SE, n = 3) in comparison to control islets (1,679 +/- 307). In contrast, IL-1 beta exposure did not significantly reduce glyburide-induced insulin secretion (1,516 +/- 231 and 1,236 +/- 214 in control and IL-1 beta-exposed islets, respectively; mean +/- SE, n = 3). When islets were simultaneously exposed to IL-1 beta and increasing concentrations of nicotinamide, a dose-dependent recovery of glucose-induced insulin secretion was observed, with the maximum effect at 25 mmol/L nicotinamide (1,007 +/- 123, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)