大鼠睾丸与腹腔Mφ的IL—1样物质活性及输精管结扎对其影响

雄性Ｗｉｓｔａｒ大鼠２１只，分为输精管结扎组（ＶＧ）和假手术组（ＳＯＧ）。术后４个月，以胸腺细胞增殖法检测腹腔Ｍφ和睾丸组织匀浆上清中ＩＬ－１样物质的活性。结果表明，（１）ＩＬ－１物质活性，随睾丸匀浆上清稀释倍数增加而增高，而不同稀释倍数的腹腔Ｍφ培养上清的各测定值均于同一水平。（２）输精管结扎对腹腔Ｍφ培养上清的ＩＬ－１样物质活性无影响，但明显地提高了睾丸匀浆上清的ＩＬ－１样物质活性。本实验结果     

IL—1对输精管结扎大鼠睾丸间质细胞功能影响的体外研究

本文观察ＩＬ－１对正常和输精管结扎大鼠睾丸间质细胞（Ｌｅｙｄｉｇｃｅｌｌｓ，莱迪希细胞）细胞功能的影响，结果表明：在人绒毛膜促性腺激素（ｈｕｎａｎｃｈｏｒｉｏｍｉｃｇｏｎａｄｏｔｒｏｐｉｎｈＣＧ）的作用下，正常和输精管结扎大鼠睾丸Ｌｅｙｄｉｇ细胞培养上清中睾酮和ｃＡＭＰ的含量均明显高于相应的对照孔，且两组比较无明显差异，说明输精管结扎后睾丸Ｌｅｙｄｉｇ细胞对垂体激素的反应性并无改变，两组细胞受ＩＬ     

睾丸IL—1β原位杂交及输精管结扎对IL—1βmRNA表达的影响

本实验成功地建立了睾丸ＩＬ－１β原位杂交技术，并在此基础上探讨了输精管结扎对睾丸ＩＬ－１β ｍＲＮＡ表达的影响，结果表明：输精管结扎６ｍｏ组家兔睾丸ＩＬ－１β ｍＲＮＡ的杂交信号明显地强于假手术对照组，而结扎２５ｍｏ组恢复同龄假手术组水平，杂交信号多分布在曲细精管内的支持细胞和生殖细胞中，有的分布在间质的细胞中，结论：输精管结扎早期睾丸产生ＩＬ－１确有明显增加，２５ｍｏ恢复对照组水平。     

输精管结扎对大鼠睾丸、附睾及血清睾酮的中长期影响

目的：建立动物模型，观测输精管结扎中、长期对血清睾酮水平及睾丸和附睾的形态学影响，为评估输精管结扎术这一男性节育主要手段提供某些基础理论依据。方法：随机将40只4月龄Wistar大鼠，按4个等长的实验间期分为结扎组和对照组，在术后第4、6、8、10月时分别测定结扎组和对照组的血清睾酮(sT)浓度及其与雄激素结合蛋白(ABP)的结合率；在对受试动物的睾丸和附睾进行组织学定性观察的同时，用TAS-plus型自动图像分析仪，对睾丸切片进行了定量组织学测定。结果：除第4月实验组和对照组外，其他3个间期的实验组和对照组血清睾酮浓度均有显著变化；实验组睾丸和附睾均有无菌性炎症发生，且未随术后时间的延长而缓解。结论：结扎术对受试动物的中长期影响值得关注。     

睾丸I-1β原位杂交及输精管结扎对IL-1β mRNA表达的影响

本实验成功地建立了睾丸ＩＬ－１β原位杂交技术，并在此基础上探讨了输精管结扎对睾丸ＩＬ－１βｍＲＮＡ表达的影响。结果表明：输精管结扎６ｍｏ组家兔睾丸ＩＬ－１βｍＲＮＡ的杂交信号明显地强于假手术对照组，而结扎２５ｍｏ组恢复同龄假手术组水平。杂交信号多分布在曲细精管内的支持细胞和生殖细胞中，有的分布在间质的细胞中。结论：输精管结扎早期睾丸产生ＩＬ－１确有明显增加，２５ｍｏ恢复对照组水平。     

扩张型心肌病IL－6及IL－1活性的初步研究

应用ＭＴＴ比色法及ＣｏｎＡ活化小鼠胸腺细胞增殖法检测了３０例扩张型心肌病（ＤＣＭ）患者及２０例正常人（ＮＣ）的血清白细胞介素６（ＩＬ－６）、白细胞介素１（ＩＬ－１）的活性，结果发现ＤＣＭ患者ＩＬ－６及ＩＬ－１活性均明显高于ＮＣ组（Ｐ＜０．００１，Ｐ＜０．０１）。提示：ＩＬ－６及ＩＬ－１功能紊乱参与了ＤＣＭ的病理过程。     

输精管结扎与吻合术后对兔睾丸细胞功能的影响

家兔31只,分为假手术对照组(C),输精管结扎组(V)和输精管吻合组,后者于结扎后12个月时行吻合术,吻合后3个月与雌兔配对交配,继续观察2个月,根据雌兔孕否再将吻合兔分为吻合育组(VaF)和吻合不育组(VaI)。结果表明,血清睾酮水平在C,VaF,VaI和V组分别是7.1±4.2,11.3±4.7,4.3±2.3和4.9±2.7nmol/L((?)±SD,下同),VaF,VaI和V组分别与C组比较差异不显差(P>0.05),而VaF和VaI组比较差异显著(P<0.01),睾丸细胞核雄激素受体浓度在C、VaF,VaH和V组分别是61.1±17.8,66.2±38.2,44.5±26.8和68.9±22.5fmol/mg.DNA,组间比较无显著差异(P>0.05);睾丸组织cAMP含量在C,VaF,VaI和V组分别是440.0±94.0,324.0±13.0,277.0±48.0和254.0±135.0pmol/g组织,VaF,VaI和V组显著低于C组(P<0.05);而睾丸胞液雄激素结合蛋白浓度分别是27.4±10.5,64.8±18.5,52.8±23.5和44.7±14.7fmol/mg·pro.,VaF,VaI和V组显著高于C组(P<0.05),睾丸细胞膜Na~ ,K~ -ATPase活性分别是78.0±28.7,62.2±10.3,43.7±9.8和32.6±10.0μmol Pi/mg·hr,VaI和V组显著低于C和VaF组(P<0.01),而Mg~(2 )-ATPase活性分别是57.2±27.0,53.6±16.2,30.9±10.9和23.1±9.1μmol Pi/mg.hr,VaI和V组显著低于VaF和C组(P<0.05,P<0.01)。     

IL—1ra对佐剂性关节炎大鼠腹腔Mφ细胞因子诱生的抑制作用

研究了ＩＬ－１ｒａ对ＡＡ大鼠腹腔Ｍφ诱生细胞因子的调节机制进行了初步探讨。结果表明ＩＬ－１ｒａ能阻断ＩＬ－１刺激的亚适剂量ＰＨＡ诱导的胸腺细胞增殖，ＩＬ－１ｒａ能显著抑制正常及ＡＡ大鼠腹腔ＭφＩＬ－１，６，８，ＴＮＦ的产生，呈剂量依赖关系，ＩＬ－１ｒａ能显著下调腹腔ＭφＩＬ－８ ｍＲＮＡ表达。提示ＩＬ－１ｒａ是一种良好的抗炎制剂。     

Functions of macrophage colony-stimulating factor (CSF1) in development,homeostasis, and tissue repair

Macrophage colony-stimulating factor (CSF1) is the primary growth factor required for the control of monocyte and macrophage differentiation, survival, proliferation and renewal. Although the cDNAs encoding multiple isoforms of human CSF1 were cloned in the 1980s, and recombinant proteins were available for testing in humans, CSF1 has not yet found substantial clinical application. Here we present an overview of CSF1 biology, including evolution, regulation and functions of cell surface and secreted isoforms. CSF1 is widely-expressed, primarily by cells of mesenchymal lineages, in all mouse tissues. Cell-specific deletion of a floxed Csf1 allele in mice indicates that local CSF1 production contributes to the maintenance of tissue-specific macrophage populations but is not saturating. CSF1 in the circulation is controlled primarily by receptor-mediated clearance by macrophages in liver and spleen. Administration of recombinant CSF1 to humans or animals leads to monocytosis and expansion of tissue macrophage populations and growth of the liver and spleen. In a wide variety of tissue injury models, CSF1 administration promotes monocyte infiltration, clearance of damaged cells and repair. We suggest that CSF1 has therapeutic potential in regenerative medicine.     

Biological activity of recombinant murine interleukin-6 in interleukin-1 T cell assays

Interleukin-6 (also called B cell stimulatory factor 2, hepatocyte activating factor, interferon-β₂) has been shown to have effects on various lineages of hemopoietic cells. Some of its activities appear to overlap those of interleukin-1. In particular, recombinant murine IL-6 induced proliferation of phytohemagglutinin-activated thymocytes, an assay widely used to detect IL-1. In this report, we compared several features of IL-1 and IL-6 dependent thymocyte proliferation. The results indicate that IL-2 is the major second mediator of both IL-1 and IL-6 dependent proliferation. Finally, we tested whether IL-6 would also have activity in other T cell-based IL-1 assays using the T cell lymphoma LBRM33 1A5 and the T cell clone D10-G4.1. IL-6 had no activity in the latter two assays. These results indicate that IL-1 assays using LBRM33 1A5 and D10-G4.1 selectively detect Il-1, and are more specific assays for the detection of IL-1 in samples that may also contain IL-6.     

失血对巨噬细胞分泌IL－1的影响及其机制分析

作者观察了失血性休克早期大鼠腹腔巨噬细胞分泌ＩＬ－１能力的变化，并初步分析其机制，发现休克后１ｈ、２ｈ巨噬细胞分泌ＩＬ－１的能力分别较失血前提高５１％及６３％，差异均有显著性。此后巨噬细胞分泌ＩＬ－１的能力逐渐降低，至休克后４ｈ较失血前下降３１％，差异有高度显著性。将不同浓度的β－ＥＰ及质皮酮分别与巨噬细胞共同培养，发现前者刺激ＩＬ－１的产生，后者抑制其分泌，均呈量效关系。实验结果提示，在失血早期巨噬细胞分泌ＩＬ－１的能力有显著变化，内源性阿片肽及糖皮质激素可能参与调节失血时巨噬细胞ＩＬ－１的分泌。     

Differential effects of interleukin-10 on the expression of HLA class II and CD1 molecules induced by granulocyte/macrophage colony-stimulating factor/interleukin-4

Interleukin (IL)-10 down-regulates HLA class II molecules, whether constitutively expressed or up-regulated by interferon-γ or IL-4 on monocytes but not on B lymphocytes. In this study we show that IL-10 does not inhibit HLA class II expression induced by the combination granulocyte/macrophage colony-stimulating factor and IL-4 on monocytes, although it simultaneously abrogates the expression of CD1 molecules induced by the same combination of cytokines. CD1 molecules can act as element of genetic restriction for CD4^? CD8^? T lymphocytes, and the suppression of CD1 expression by IL-10 abolished antigen presentation to CD1-restricted CD4^? CD8^? T cell receptor-positive T cells. Although HLA class II expression was not down-regulated by IL-10, the antigen specific proliferative response of CD4⁺ T cells was nevertheless decreased. This was not caused by down-regulation of known co-stimulatory molecules such as B7.1, B7.2 and ICAM-1. IL-10 decreased the antigen specific proliferative response further by directly influencing the T lymphocytes. Our results indicate that IL-10 exerts some of its immunoregulatory functions by differential modulation of antigen presenting molecules, induced by the same combination of cytokines.     

同型半胱氨酸对人THP-1巨噬细胞IL-8 mRNA及其蛋白表达的影响

目的:探讨同型半胱氨酸(Hcy)对人THP-1巨噬细胞IL-8 mRNA的表达和IL-8分泌的影响。方法:在由0.1 μmol/L佛波脂(PMA)诱导分化的人THP-1巨噬细胞中加入不同浓度的Hcy,并孵育不同时间。用酶联免疫吸附法(ELISA)检测培养上清液中IL-8蛋白的含量,用半定量RT-PCR法检测IL-8 mRNA表达。结果:经PMA诱导后,THP-1细胞贴壁生长,分化成巨噬细胞。在一定浓度范围之内,Hcy呈剂量依赖性刺激THP-1巨噬细胞分泌IL-8蛋白,0.05 mmol/L Hcy即可促进其分泌增加为对照组的1.28倍(P<0.01);0.20 mmol/L Hcy使IL-8的产量增加到对照组的1.55倍(P<0.01)。0.10 mmol／L Hcy干预后,IL-8蛋白在3 h即高于对照组,到48 h仍明显高于对照组。半定量RT-PCR结果也显示Hcy能刺激IL-8 mRNA表达,呈剂量和时间依赖关系。结论:Hcy能促进人THP-1巨噬细胞IL-8 mRNA表达和分泌IL-8蛋白。这可能为其诱导动脉粥样硬化的重要机制之一。     

输精管结扎4月大鼠血清与前列腺组织的前列腺酸性磷酸酶活力变化

成年Ｗｉｓｔａｒ大鼠２０只，随机分为输精管结扎组（ＶＧ）和假手术组（ＳＯＧ）。术后第４个月检测了前列腺酸性磷酸酶（ＰＡＰ）等代表前列腺功能与肿瘤标志的酶学指标。结果表明，（１）血清ＰＡＰ活力，ＶＧ为４．９６±３．４Ｕ／ｍｌ，ＳＯＧ为５．６３±１．６９Ｕ／ｍｌ，两组无显著差异（Ｐ＞０．０５）；ＶＧ前列腺组织ＰＡＰ活力（１８．００±８．８１Ｕ／ｇ）略高于ＳＯＧ的（１５．０４±１１．９０Ｕ／ｇ），但无显著性。Ｐ／Ｔ百分比值ＶＧ为６５．０２±２５．３６％，ＳＯＧ为６８．６５±１１．６５％，Ｐ大于０．０５。（２）血清与前列腺组织碱性磷酸酶（ＡＬＰ）、乳酸脱氢酶（ＬＤＨ）与磷酸肌酸激酶（ＣＫ）活力，两组均无显著差异（Ｐ＞０．０５）。     

Simple, sensitive and specific bioassay of interleukin-1

This paper describes a convenient method for the culture of sub-lines of the murine T cell cloned line, D10.G4.1, and the use of these lines in a highly sensitive and specific bioassay for interleukin-1 (IL-1). The cells are cultured with IL-1, interleukin-2 (IL-2), and concanavalian A (ConA), in the absence of feeder cells or antigen. Assays are routinely carried out in the presence of saturating IL-2, which enhances sensitivity and ensures that further IL-2 will not give false positives. Addition of interleukin-4 (IL-4) has a similar effect and can be used together with IL-2 where there is a potential for interference from either cytokine. The assay is not affected by high concentrations of human interleukin-6 or tumour necrosis factor- (TNF-) and only minimally affected by high concentrations of murine TNF-.     

Grcadian rhythm of interleukin-1 production of monocytes and the influence of endogenous and exogenous glucocorticoids in man

Summary We found a dose-dependent inhibition of spontaneous and LPS-induced IL-1 production of isolated human monocytes by methylprednisolone (MP) in vitro. Kinetic studies of spontaneous and LPS-induced IL-1 production of isolated monocytes of 10 normal individuals showed a synchronous circadian rhythm, with its maximum at 4:00 p.m. and its minimum at 4:00 a.m., which is most probably independent of the physiological circadian rhythm of cortisol levels because the IL-1 production was of the same value at the times of maximum and minimum cortisol levels. In contrast, in a patient with hypercortisolism and a preserved circadian rhythm of cortisol levels, we found the minimum of IL-1 production at 4:00 p.m., 8 hours after the maximum cortisol level was reached. Furthermore, in 7 patients with sarcoidosis both spontaneous and LPS-induced IL-1 production of isolated monocytes were significantly decreased 8 hours after the first injection of MP (1 mg/kg bw i.v.) compared to the values before MP administration. Our findings suggest a physiological circadian rhythm of spontaneous and LPS-induced IL-1 production of monocytes, independent of physiological cortisol levels, whereas unphysiological amounts of endogenous and exogenous glucocorticoids cause a substantial inhibition of IL-1 production with a latency time of 8 hours.Abbreviations IL-1 interleukin 1 - IL-2 interleukin-2 - LPS lipopolysaccharide - MP methylprednisolone - CBP corticoid-binding protein     

Soluble CD23 potentiates interleukin-1-induced secretion of interleukin-6 and interleukin-1 receptor antagonist by human monocytes

The low-affinity receptor for IgE (CD23) is cleaved into biologically active soluble fragments (sCD23), some of which have been reported to exhibit pleiotropic activities. However, it is not known whether the sCD23 fragments contribute to the induction and/or regulation of pro-inflammatory cytokine production. In this study, this possibility was tested using interleukin (IL)-1-stimulated human whole blood as an ex vivo model of cytokine cascade production. We show that human recombinant 25-kDa sCD23 significantly enhanced the production of IL-6 in whole blood stimulated by IL-1, but had only little or no effect in the absence of IL-1. The potentiating effect of sCD23 was concentration dependent within the range of plasma levels occurring during various inflammatory processes in man. These results prompted us to study whether sCD23 and IL-1 together also enhance the production of regulating factors exhibiting anti-cytokine activities. Our data indicate that sCD23 augments the release of IL-1 receptor antagonist induced by IL-1. Finally, examining the effect of sCD23 on human peripheral monocytes stimulated by IL-1, we confirmed the capacity of sCD23 to potentiate cytokine production. We suggest that sCD23 can modulate monocyte functions, thereby contributing to the amplification and regulation of immune and inflammatory processes.