Fever and feeding in the rat: Actions of intrahypothalamic interleukin-6 compared to macrophage inflammatory protein-1β (MIP-1β)

The chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1β, induce an intense fever in the rat when they are injected directly into the anterior hypothalamic, pre-optic area (AH/POA), a region containing thermosensitive neurons. The purpose of this study was to compare the central action on body temperature (T_b) of MIP-1β with that of interleukin-6 (IL-6), which also has been implicated in the cerebral mechanism underlying the pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of guide cannulae for repeated micro-injections, radio transmitters which monitor T_b continuously were inserted intraperitoneally in each of 15 male Sprague-Dawley rats. Each micro-injection was made in a site in the AH/POA in a volume of 1.0 μl of pyrogen-free artificial CSF, recombinant murine MIP-1β, or recombinant human IL-6. MIP-1β in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in T_b of 2.4 ± 0.21°C reached by 3.7 ± 0.42 hr, and a duration exceeding 6.5 hr. Injected into homologous sites in the AH/POA, IL-6 induced a dose dependent fever of similar latency and a mean maximal increase in T_b of 1.2 ± 0.25°C, 1.8 ± 0.15°C, and 2.1 ± 0.22°C and duration of 6.2 ± 1.28 hr, 6.7 ± 0.49 hr, and 6.8 ± 0.65 hr when given in doses of 25, 50, and 100 ng, respectively. These results show that MIP-1β and the highest dose of IL-6 induce a fever of comparable intensity, but MIP-1β exerts its action in a much lower concentration. Thus, the de novo synthesis and subsequent action of the MIP-1 family of cytokines on neurons of the AH/POA in response to a pyrogen challenge apparently play a functional role in the pathogenesis of fever. Further, the endogenous activity of IL-6 in the hypothalamus which is enhanced in response to a lipopolysaccharide also may reflect its essential part in the acute phase response to a bacterial challenge. Copyright © 1994 Wiley-Liss, Inc.     

Unilateral lesion of the nigrostriatal pathway decreases the firing rate and alters the firing pattern of globus pallidus neurons in the rat

Activities of spontaneously firing neurons in the globus pallidus of intact rats and rats that survived unilateral lesions of the nigrostriatal pathway for 3 days, 1 week, or 6-11 weeks were compared. No significant differences in neuronal firing rate, firing pattern, and number of cells per pass were observed between chloral hydrate-anesthetized control and lesioned animals. However, in locally anesthetized animals, pallidal cells fired significantly faster than in chloral hydrate-anesthetized animals, and the lesion caused a decrease in the firing rates of pallidal cells 1 week and 6-9 weeks postlesion. In addition, significant differences in the firing pattern of pallidal cells, as determined by the ratio of the mean to median interspike intervals, were seen between locally anesthetized controls and animals surviving 3 days, 1 week, and 6-9 weeks postlesion. This altered firing pattern tended to return to normal with time. The number of cells per pass was not significantly altered by the lesion. Data from this study suggest that, in locally anesthetized animals, the removal of the tonic dopaminergic input to the basal ganglia causes pallidal cells to decrease their firing rates in a time-dependent fashion and causes reversable firing pattern changes. This suggests that tonically active dopamine neurons, probably acting through the striatopallidal pathway, regulate the firing rate and mechanisms controlling the temporal ordering of spontaneous discharges of globus pallidus neurons.     

Serum levels of interleukin-6 and tumour-necrosis-factor-alpha are not correlated to disease activity in patients with rheumatoid arthritis after treatment with low-dose methotrexate

Abstract. Cytokines are major mediators of inflammatory responses in rheumatoid arthritis. Some of them have been shown to correlate with the disease activity and thus are proposed to be used for monitoring patients. Therefore the effects of a low-dose therapy with methotrexate on serum concentrations of interleukin-6 (IL-6) and tumour-necrosis-factor-alpha (TNF-α) were examined in eight patients with seropositive rheumatoid arthritis. Serum levels of IL-6 and TNF-α were significantly elevated in patients compared to healthy controls. Before the onset of MTX treatment IL-6 concentrations were correlated to the c-reactive protein ( P < 0·05) but the correlation was abolished after treatment. For TNF-α no correlations neither before nor after treatment were observed. Both cytokines remained substantially elevated after MTX treatment despite a clear reduction in disease activity. Thus we suggest that one of the effects of MTX might be the inhibition of some of the actions of IL-6 and TNF-α.     

原发性胆囊癌CD44v6和bcl-2的表达及其与临床病理的关系

目的　探讨CD44v6和bcl 2蛋白在原发性胆囊癌组织中的表达及其与癌组织类型、病理分级和转移状况的关系 ,以及CD44v6表达与bcl 2表达的相关性。方法　应用免疫组织化学方法检测 50例原发性胆囊癌、2 0例胆囊腺瘤和 1 0例慢性胆囊炎组织中CD44v6和bcl 2蛋白的表达。结果　胆囊癌组织中CD44v6和bcl 2表达阳性率分别为82 .0 %和 60 .0 % ,均明显高于胆囊腺瘤 (分别为 45 .0 %和 30 .0 % ,P<0 .0 5) ,并随着胆囊癌细胞分化程度的减低、病理分级的增高和转移而明显增高 (P<0 .0 5)。同时 ,CD44v6的表达与bcl 2表达呈正相关 (r =0 .36 ,P<0 .0 5)。结论　CD44v6和bcl 2均是胆囊癌高度恶性和预后不良的重要指标。胆囊癌CD44v6表达与bcl 2蛋白表达可能具有相互协同作用。     

RP－HPLC法测定复合维生素B片中维生素B_1、B_2、B_6和烟酰胺的含量

用ＲＰ－ＨＰＬＣ法（固定相为μＢｏｎｄｐａｋ Ｃ１８柱，流动相为己烷磺酸钠冰醋酸液，紫外检测波长为２８０ｎｍ）同时测定出复合维生素Ｂ片中四个组分的含量，方法专属性强，省时；维生素Ｂ１、Ｂ２、Ｂ６和烟酰胺的平均回收率和平均相对标准偏差分别为１００．５％，２．０％；９８．０％，１．９％；１０１．８％，１．１％；１００．１％，２．１％（ｎ＝３）。     

恙虫病东方体在无生命培养基内生长的研究

目的　恙虫病东方体 (Orientiatsutsugamushi;Ot)被认为属专性细胞内寄生。特别是制备大量抗原培养难的问题 ,是近一个世纪以来人们渴望解决的难题。为证实是否能在无生命培养基生长。方法　用Vero -E6个单层组织细胞培养OtJL - 90株与标准Gilliam株 ,在合适时取该培养物接种于Ⅲ号无生命固体培养基培养 ,置 36℃ (± 1℃ )培养 18- 2 4h。结果　可见生长一群无色透明或半透明光滑、湿润、圆形或枫叶样小菌落 ,并产生一种难闻的臭味。两种方法培养物分别做了生物学性状鉴定、形态染色、小白鼠致病力、血清学特异性间接免疫荧光检测。各株Ot经两种培养获得培养物特性基本一致。结论　Ot能在细胞内生长也能在无生命培养基内生长 ,解决了Ot大量抗原培养难的困扰。     

原发性胆囊癌CD44v5、CD44v6表达及其临床病理意义的研究

目的 检测胆囊癌组织中CD44v5、CD44v6的表达,并探讨其在胆囊癌发生发展过程中的临床病理意义.方法 采用SP免疫组织化学方法,检测49例胆囊癌、10例胆囊结石伴慢性胆囊炎组织和10例正常胆囊组织中CD44v5、CD44v6蛋白表达情况.结果 CD44v5、CD44v6阳性表达率在胆囊癌组织明显高于良性组织.在胆囊癌中,CD44v5基因表达阳性率与组织学分级无关,CD4 4v6基因表达阳性率与组织学分级有关.有淋巴结转移的胆囊癌组织中,CD44v5、CD44v6阳性表达率明显高于无淋巴结转移者.结论 CD44v5、CD44v6可能在胆囊癌的淋巴结转移中起着重要的作用,CD44v5、CD4 4v6可能是了解胆囊癌病变发生发展生物学行为,淋巴结转移的重要生物学指标.     

Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma

Background and Aims: Chemokines and their receptors have recently been shown to have major roles in cancer metastasis. The aim of this study was to determine whether the interaction between chemokine receptor 6 (CCR6) and its ligand, macrophage inflammatory protein‐3 alpha (MIP‐3α), correlates with metastasis of hepatocellular carcinoma (HCC). Methods: To observe the reaction of CCR6 expressed cancer cells to MIP‐3α stimulation, chemotactic and actin polymerization assays for both CCR6 high cells (HepG2) and CCR6 low cells (MCF‐7) were performed. CCR6 mRNA levels in tumor specimens from 30 HCC patients were quantified by real‐time polymerase chain reaction. Patients were classified into two groups, high (≥ 20 copies; n = 10) CCR6 and low (<20 copies; n = 20) CCR6 on the basis of CCR6 expression, and the groups were compared with respect to clinicopathological features. Results: When HepG2 cells (CCR6 high) were stimulated with MIP‐3α, they migrated in a dose‐dependent manner, and formation of pseudopodia was observed. These phenomena were not observed in the CCR6 low cells. The incidence of intrahepatic metastasis was higher in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Disease‐free survival was significantly poorer in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Conclusions: It was indicated that CCR6 might be associated with intrahepatic metastasis of HCC and might be able to become one of the prognostic factor after hepatic resection for HCC.