Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones

The production and action of immunoregulatory cytokines, including interleukin-1 (IL-1), are inhibited by glucocorticoid hormones in vivo and in vitro. Conversely, glucocorticoid blood levels were increased by factors released by human leukocytes exposed to Newcastle disease virus preparations. This activity was neutralized by an antibody to IL-1. Therefore the capacity of IL-1 to stimulate the pituitary-adrenal axis was tested. Administration of subpyrogenic doses of homogeneous human monocyte-derived IL-1 or the pI 7 form of human recombinant IL-1 to mice and rats increased blood levels of adrenocorticotropic hormone (ACTH) and glucocorticoids. Another monokine, tumor necrosis factor, and the lymphokines IL-2 and gamma-interferon had no such effects when administered in doses equivalent to or higher than those of IL-1. The stimulatory effect of IL-1 on the pituitary-adrenal axis seemed not to be mediated by the secondary release of products from mature T lymphocytes since IL-1 was endocrinologically active when injected into athymic nude mice. These results strongly support the existence of an immunoregulatory feedback circuit in which IL-1 acts as an afferent and glucocorticoid as an efferent hormonal signal.     

Inhibition of adrenocorticotropic hormone secretion in the rat by immunoneutralization of corticotropin-releasing factor

Intravenous administration of rabbit antiserum to ovine corticotropin-releasing factor (CRF) markedly reduced the CRF-induced rise of plasma adrenocorticotropic hormone (ACTH) in intact nonstressed adult male rats while blocking more than 75 percent of the ACTH release observed in rats exposed to ether stress. Furthermore, antiserum to CRF significantly lowered ACTH levels in adrenalectomized animals. These results suggest that endogenous CRF plays a physiological role in regulating ACTH secretion.     

Beta-adrenergic mechanism of insulin-induced adrenocorticotropin release from the anterior pituitary

Intraperitoneal administration of insulin to control rats and to rats with pituitary stalk transections or with lesions of the median eminence resulted in increased plasma adrenocorticotropin (ACTH) levels. The insulin-induced stimulation of ACTH release was blocked in both the control and lesioned animals by prior treatment with either the beta-adrenergic antagonist propranolol or the glucocorticoid analog dexamethasone. The direct application of insulin to primary cultures of the anterior pituitary did not evoke ACTH release or affect the maximal ability of corticotropin-releasing factor or epinephrine to stimulate ACTH secretion. The results suggest that insulin stimulates ACTH release by a mechanism in which catecholamines of peripheral origin act directly on the anterior pituitary.     

Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor

There is now evidence that the immune system, during times of infectious challenge, can stimulate the secretion of glucocorticoids, the adrenal steroids that mediate important aspects of the response to stress. Specifically, secretion of interleukin-1 (IL-1), a monocyte lymphokine secreted after infection, appears at least in part responsible for this effect. Glucocorticoids are secreted in response to a neuroendocrine cascade involving, first, the brain, then the pituitary, and finally the adrenal gland. In this report, human IL-1 is shown to activate the adrenocortical axis at the level of the brain, stimulating the release of the controlling hormone corticotropin-releasing factor (CRF) from the hypothalamus. Infusion of IL-1 induced a significant secretion of CRF into the circulation exiting the hypothalamus, whereas immunoneutralization of CRF blocked the stimulatory effect of IL-1 on glucocorticoid secretion. IL-1 appeared to have no acute direct stimulatory effects on the pituitary or adrenal components of this system. Furthermore, IL-1 did not cause a nonspecific release of other hypothalamic hormones. Thus, the lymphokine acts in a specific manner to activate the adrenocortical axis at the level of the brain; this effect appears to be unrelated to the known pyrogenic effects of IL-1 within the hypothalamus.     

Stress-induced inhibition of reproductive functions: role of endogenous corticotropin-releasing factor

In the adult castrated male rat, exposure to inescapable, intermittent electroshocks inhibited the pulsatile pattern of luteinizing hormone release and markedly lowered its plasma concentrations. The central administration of the corticotropin-releasing factor (CRF) antagonist alpha-helical ovine CRF residues 9 to 41 reversed the inhibitory action of stress. Neither its peripheral injection, nor the intraventricular injection of the inactive CRF analog des-Glu to Arg ovine CRF was effective. These results suggest that endogenous CRF may mediate some deleterious effects of noxious stimuli on reproduction.     

柴术抗激颗粒对LPS诱导大鼠神经-内分泌-免疫相关因子调节机制研究

【目的】“仔猪早期断奶应激综合征”给养猪业带来了巨大的经济损失。中药制剂柴术抗激散(CZKJS)通过现代制药技术制成柴术抗激颗粒(CZKJKL),已被证实其对早期断奶仔猪应激及早期断奶仔猪脂多糖（LPS）免疫应激都具有明显的缓减作用。现进一步探究CZKJKL对LPS免疫应激断奶大鼠应激相关神经递质、细胞因子和HPA轴相关激素的影响,从机理上证实其抗应激作用。【方法】选取体重相近的18日龄断奶的Wistar大鼠72只,随机分为3个处理组,即Ⅰ组（空白对照组）、Ⅱ组（LPS免疫应激模型组）、Ⅲ组（LPS+CZKJKL组）。每个处理设6个重复,每个重复4只。在18-24日龄期间,Ⅲ组的大鼠每天灌服5 000 mg·kg^-1BW柴术抗激颗粒,Ⅰ组、Ⅱ组的大鼠每天灌服等剂量生理盐水;21日龄时,Ⅱ组、Ⅲ组的大鼠腹腔注射4 mg·kg^-1BW的LPS,Ⅰ组的大鼠腹腔注射等剂量生理盐水,注射后6 h采血并取样。测定指标有：①海马：去甲肾上腺素(NE)和5-羟色胺(5-HT);②下丘脑：β-内啡肽（β-EP）和促肾上腺皮质激素释放因子（CRF）;③血清：β-内啡肽(β-EP)、促肾上腺皮质激素(ACTH)、皮质醇(COR)、白介素-1β (IL-1β)、白介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)、一氧化氮(NO)、诱导性一氧化氮合酶(iNOS)。【结果】与Ⅰ组相比,Ⅱ组大鼠海马NE和5-HT的含量均极显著升高（P＜0.01）,下丘脑β-EP的含量极显著升高（P＜0.01）,血清β-EP、IL-1β、IL-6、TNF-α、NO、ACTH、COR的含量均极显著升高（P＜0.01）,血清iNOS的活性极显著增强（P＜0.01）。与Ⅱ组相比,Ⅲ组大鼠海马NE和5-HT的含量均极显著降低（P＜0.01）,下丘脑β-EP的含量极显著降低（P＜0.01）,血清β-EP、IL-1β、IL-6、TNF-α、NO、ACTH、COR的含量均极显著降低（P＜0.01）,血清iNOS的活性极显著减弱（P＜0.01）。【结论】CZKJKL可通过有效调节LPS免疫应激状态下机体神经-内分泌-免疫系统相关神经递质、细胞因子和HPA轴激素的紊乱而发挥其抗免疫应激作用。     

Calcium as a coagonist of inositol 1,4,5-trisphosphate-induced calcium release

Inositol 1,4,5-trisphosphate (IP3)-induced calcium release from intracellular stores is a regulator of cytosolic-free calcium levels. The subsecond kinetics and regulation of IP3-induced calcium-45 release from synaptosome-derived microsomal vesicles were resolved by rapid superfusion. Extravesicular calcium acted as a coagonist, potentiating the transient IP3-induced release of calcium-45. Thus, rapid elevation of cytosolic calcium levels may trigger IP3-induced calcium release in vivo. Extravesicular calcium also produced a more slowly developing, reversible inhibition of IP3-induced calcium-45 release. Sequential positive and negative feedback regulation by calcium of IP3-induced calcium release may contribute to transients and oscillations of cytosolic-free calcium in vivo.     

混料设计法在控释肥配比中的应用研究

采用混料试验设计,探讨了包含多种供肥速度的速度复合型控释肥和单一供肥速度的单一速度型控释肥的养分释放速率。结果表明:(1)单一速度型控释肥(FP2,FP5和FP9)在养分快速释放期内,养分释放速率基本保持不变,其顺序为FP2>FP5>FP9;而对于速度复合型控释肥处理,其释放速率不是单一、固定不变的。(2)在培养-淋溶期间,对养分累积释放率≥30.0%的单一速度型控释肥料因子优化组合进行频数统计,发现控释肥FP2,FP5和FP9的混料比例分别为37.61%～45.02%,32.68%～40.83%和21.85%～23.94%。(3)模拟各肥料处理养分累积释放率的Richards函数方程的复相关系数均达到极显著水平,表明使用Richards方程能够准确地描述和预测养分的释放速率。     

控释掺混肥对大蒜根际土壤酶活性的影响

通过大田试验系统研究了控释掺混肥（crf）对大蒜根际土壤酶活性的影响。结果显示土壤酶活性（土壤脲酶、磷酸酶、蔗糖酶和过氧化氢酶）随控释掺混肥施入量的增加而显著提高,等量（crf1）和80%用量（crf2）处理脲酶、磷酸酶和蔗糖酶活性均显著高于普通施肥（ccf）处理,表明控释掺混肥可通过增强土壤酶活性来提高土壤速效养分含量,进而提高大蒜鳞茎产量。     

ACTH肌注建立鸡免疫抑制模型及其评价

连续7 d给鸡肌肉注射不同剂量(15、30、45 IU·kg-1·d-1)的ACTH(adrenocorticotropic hormone)后,通过生理学和免疫学指标对该模型进行了评价。结果显示,45 IU·kg-1·d-1处理组的血清皮质酮浓度、肾上腺指数均显著高于对照组(P<0.05);而血清IgG、IgA、IL-2、IFN-γ水平,胸腺、脾脏和法氏囊指数,组织IgG和禽β-防御素6生成量均显著低于对照组(P<0.05);处理组的血糖值仅在注射ACTH后2 h显著高于对照组(P<0.05),其他时间差异不显著。本研究表明,15、30、45 IU·kg-1·d-1的ACTH连续7 d肌肉注射可引起鸡应激性免疫抑制。血清皮质酮升高、肾上腺肥大和肾上腺皮质细胞增生肥大可用于评价持续应激,而血糖不适合评价持续应激;免疫抑制评价指标包括免疫器官萎缩,组织中免疫细胞数量、IgG和禽β-防御素6生成量下降,以及血清IgG、IgA、IFN-γ和IL-2水平降低。     

包膜控释肥料氮素释放动力学研究

采用7d静置法和土壤培养试验,对聚合物包膜控释肥料养分释放动态进行了研究。结果表明,供试的7种包膜肥料初期溶出率均小于12%,微分溶出率为0.26%～2.49%;培养期间,7种肥料配比的养分释放曲线斜率均随时间的延长而逐渐下降;养分释放曲线根据其斜率可分为3组:2种控释肥单施或配合施用的最低,单施尿素的最高,尿素与控释肥配合施用的居中;各处理的氮释放动力学方程均达到显著或极显著水平,可用一级动力学方程描述其养分释放特性;速率常数k既可反映控释肥料氮素释放速率的快慢,又可描述肥料的配比效应。与控释肥单施或其配合施用相比,尿素与控释肥配比施用,氮素释放速率增加了65.4%～164.5%,释放期缩短了11～44d。     

Release of multiple hormones by a direct action of interleukin-1 on pituitary cells

Exposure to bacterial endotoxins has long been known to stimulate the release of anterior pituitary hormones; administration of endotoxin was at one time a common clinical test of anterior pituitary function. Endotoxin is a potent stimulus for production of the endogenous pyrogenic protein, interleukin-1 (IL-1), by macrophages and monocytes. The possibility that IL-1 has a direct effect on the secretion of hormones by rat pituitary cells in a monolayer culture was investigated. Recombinant human IL-1 beta stimulated the secretion of adrenocorticotropic hormone, luteinizing hormone, growth hormone, and thyroid-stimulating hormone. Increased hormone secretion into culture supernatants was found with IL-1 concentrations ranging from 10(-9) M to 10(-12) M. Prolactin secretion by the monolayers was inhibited by similar doses. These concentrations of IL-1 are within the range reported for IL-1 in serum, suggesting that IL-1 generated peripherally by mononuclear immune cells may act directly on anterior pituitary cells to modulate hormone secretion in vivo. Incubation of IL-1 solutions with antibody to IL-1 neutralized these actions. These pituitary effects of IL-1 suggest that this monokine may be an important regulator of the metabolic adaptations to infectious stressors.     

缓/控释复合肥料不同形态氮素释放特性研究

【目的】探讨缓/控释复合肥料不同形态氮素养分（NH4+-N、NO3－-N、Urea-N、DON和Total N）在不同介质中释放的动力学特性及生物效应。【方法】采用水中溶出法、土壤恒温培养法和盆栽生物试验。【结果】不同培养介质中，缓/控释复合肥5种形态氮素养分的累积释放量随时间的动态变化可用一级动力学方程Nt=N0(1-e-kt）、Elvoich方程qt=a+blnt、抛物线扩散方程qt=a+bt0.5表征，并以一级动力学方程拟合效果最好（r＝0.9569**～0.9999**），E1ovich方程次之（r＝0.7705**～0.9933**）。缓释复合肥料不同形态氮素最大释放量（N0值）与其氮素累积释放量的变化规律一致，在水中以Total N＞DON＞Urea-N＞NH4+-N＞NO3--N，在土壤中则以Total N＞NH4+-N＞DON＞Urea-N＞NO3--N。以水为介质时，缓释复合肥料不同形态氮素释放速率常数（k值和b值）的变化序列均以Total N＞DON＞NH4+-N＞NO3--N；以土壤为介质时，k值大小为Urea-N＞DON＞NH4+-N＞Total N＞NO3--N，b值则为Total N＞NH4+-N＞DON＞NO3--N＞Urea-N。与普通复合肥料相比，缓/控释复合肥的氮素利用效率（NUE）、氮素农学效率（NAE）及氮素生理效率（NPE）分别提高了11.4%、8.32 kg·kg-1和5.17 kg·kg-1。相关分析发现，5种形态氮素养分占总氮量的比值（Nx/NT）与水稻不同生育期吸收氮素养分之间呈显著或极显著正相关。【结论】定量描述氮素养分释放的动力学方程中以一级动力学方程评价更具有实效性。与普通复合肥料以单一尿素态氮养分为主相比较，缓/控释复合肥料的不同形态氮养分更有利于水稻对氮素的吸收利用。     

松花苦桑粉对糖尿病小鼠降血糖的作用

[目的]研究松花苦桑粉的降血糖作用,为其作为辅助降血糖的功能食品提供科学依据。[方法]以正常小鼠、四氧嘧啶(ALX)诱导的糖尿病模型小鼠为材料,按体重随机分组,灌胃给药,测定空腹血糖,进行淀粉负荷糖耐量试验(OSTT)。[结果]松花苦桑粉以13.6、6.6、3.3 g/kg 3种剂量灌胃15 d,以13.6 g/kg剂量效果为好,具有统计学意义(P<0.01)。松花苦桑粉以13.6、6.6、3.3 g/kg 3种剂量灌胃35 d,其中13.6 g/kg剂量组ALX性糖尿病小鼠空腹血糖显著降低(P<0.05);高、中和低剂量组均明显降低ALX性糖尿病小鼠血糖水平。[结论]在空腹血糖试验,松花苦桑粉降低正常小鼠空腹血糖试验结果阳性,降低ALX性糖尿病小鼠空腹血糖试验结果阳性。在糖耐量试验,松花苦桑粉对ALX性糖尿病小鼠的糖耐量试验结果阳性。13.6、6.6和3.3 g/kg松花苦桑粉对ALX性糖尿病小鼠的糖耐量试验结果阳性。     

控释BB肥在苹果苗圃育苗上的经济效益

[目的]研究了控释BB肥对苹果嫁接苗生长和经济效益的影响。[方法]通过大田试验,比较控释BB肥与普通肥料的施用效果。[结果]施肥量相同的SF与CRF1处理相比较,CRF1处理嫁接苗质量、经济效益在0.05水平显著高于SF处理;即使减少肥料的施用量,CRF2、CRF3处理嫁接苗质量和经济效益仍不低于SF处理。因此,从培育优良的苹果嫁接苗的角度考虑,控释肥推荐施肥量为630-150-480 kg/hm2;从减少肥料投入、增加经济效益的角度考虑,控释肥推荐施肥量为504-120-384 kg/hm2。[结论]该研究可为控释肥在苹果苗圃育苗上的合理施用提供技术指导。     

The TLR Expression Pattern on Monocyte-Derived Macrophages for Lipopolysaccharid Stimulation of Calves

In this paper, toll-like receptor expression pattern in monocytes-derived macrophages by lipopolysaccharid （LPS） stimulation was examined. Jugular venous blood samples from 4 Japanese calves were obtained and the peripheral blood mononuclear cells （PBMC） were isolated. The PBMC were cultured for 7 d so as to collect monocytes-derived macrophages in Repcell. The PBMC were stimulated by LPS for 24 h and the mRNA expression pattern of TLR and cytokines in monocytes-derived macrophages （Mod-Mφ） was analyzed. Results showed that LPS stimulation of Mod-Mφ could increase the mRNA levels of the genes of TNF-α, IL-6, and IL-8. In addition, the mRNA levels of the genes of TNF-α and IL-6 in the group of LPS stimulation were most significantly （P 〈 0.01） higher than those in control group and the mRNA levels of TLR1, 3, 5, 8, and 10 were significantly （P 〈 0.05） decreased after LPS stimulation. There was no difference in the mRNA expressions of TLR2, 4, 6, and 7 between the groups of the control and LPS stimulation. Besides, expression of TLR9 was not found. It suggested that monocytes-derived macrophages could respond to LPS and they might take an important role in the innate immunity. The important function of the cells might contribute to better disease treatment.     

RESEARCH ARTICLE Effects of Central Administration of Glutamine and Alanine on Feed Intake and Hypothalamic Expression of Orexigenic and Anorexigenic Neuropetides in Broiler Chicks

Different amino acids have been shown to affect feed intake when injected directly into the central nervous system of birds. In the present study, we investigated the effects of L-glutamine and L-alanine on feed intake and the mRNA expression levels of hypothalamic neuropeptides involved in feed intake regulation in broiler chicks. L-Glutamine or Lalanine was intra-cerebroventricularly (ICV) administered to 4-d-old broiler chicks and the feed intake were recorded at various time points. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of neuropeptide Y (NPY), agouti related protein (AgRP), pro-opiomelanocortin (POMC), melanocortin receptor 4 (MC4R) and corticotropin releasing factor (CRF). Our results showed that ICV administration of L-glutamine (0.55 or 5.5 μmol) significantly increased feed intake up to 2 h post-administration period and the hypothalamic NPY mRNA expression levels, while it markedly decreased hypothalamic POMC and CRF mRNA expression levels. In contrast, ICV administration of L-alanine (4 μmol) significantly decreased feed intake for the first 0.5 h post-administration period, and reduced the hypothalamic AgRP mRNA expression levels, while it remarkablely enhanced the mRNA expression levels of MC4R and CRF. These findings suggested that L-glutamine and L-alanine could act within the hypothalamus to influence feed intake in broiler chicks, and that both orexigenic and anorexigenic neuropeptide genes might contribute directly to these effects.     

控释肥对苹果幼树生长发育的影响

试验研究了控释肥对苹果幼树土壤有机质和pH值、叶片矿质元素和叶绿素含量以及新梢生长量的影响.结果表明,施肥降低了果园土壤的pH值和有机质含量,施用控释肥果园的pH值要高于普通复合肥,不同控释肥处理差异不明显;控释肥提高了叶片N、P和K的含量,控释肥CRF1处理的叶片N、P、K含量比普通复合肥处理分别高出7.6％、3.3％和11.4％;CRF1控释肥提高了苹果叶片中Ca、Mg、Cu和Mn的含量,降低了Fe和Zn的含量;控释肥处理明显提高了叶片叶绿素含量,不同控释肥处理之间差异不明显.     

Influence of Radix scutellariae on Th1/Th2 cytokine balance in RU486-induced abortion in mice

The aim of this study is to investigate the significance of Th1/Th2 cytokine balance in the uterus in the early embryo loss (or resorption), and to elucidate immunological modulation at the maternal-fetal interface with Chinese herbal medicine Radix scutellariae (Huang Qin) and its constituents (Baicalin and Baicalein). Mifepristone (RU486) was given via subcutaneous injection in the scapular area to induce abortion in mice at day 7 of gestation. The levels of uterine Th1 cytokines (IFN-γ, IL-2) and Th2 cytokines (IL-4, IL-10) were analyzed by enzyme-linked immunosorbent assay (ELISA), respectively. The mean values of Th1 cytokines in the uterus of RU486-treated abortion mice were significantly higher (P < 0.05) than that of the control mice, but no significant difference was observed regarding to the contents of Th2 cytokines of different groups (P > 0.05). However, when the Radix scutellariae and its constituents were used to prevent RU486-induced abortion, the levels of IFN-γ and IL-2 decreased while that of IL-4 and IL-10 increased. The embryo loss induced by RU486 was closely related to the Th1/Th2 immune balance at the maternal-fetal interface. Radix scutellariae and its constituents have an anti-abortive effect through restoring the Th1/Th2 balance at the maternal-fetal interface.     

茶树专用控释肥在幼龄茶园的肥效研究

在山东两年生幼龄茶园中分别施用金正大茶树专用控释肥CRF1（N—P2O5-K2O=25—4-11）、CRF2（N—P2O5-K2O=20—6—14）和普通肥料CCF（尿素＋复合肥＋碳酸氢铵）,其中CCF处理年施入纯氮量为100．8kg／hm2,CRF1处理设置3个水平CRF1—1、CRF1—2和CRF1—3,其肥料施用量按纯氮计算分别为CCF的100％、80％、50％;CRF2处理设置2个水平CRF2—1、CRF2—2,其肥料施用量按纯氮计算分别为CCF的100％、50％。大田试验结果表明：（1）、CRF1—1和CRF2—1在春、夏季显著提高土壤中有效氮、磷、钾含量;但在秋季,所有处理均表现出营养元素供应不足的现象;（2）、控释肥处理能显著增强茶树光合速率,增加百芽重,同时提高氨基酸含量,降低酚／氨比,进一步提高山东绿茶品质;（3）、山东幼龄茶园肥料施用量偏少．席在CR砣-1处坪的基础上继续试验来确定最佳浓肥量．