Influence of IFNα-2b and BCG on the release of TNF and IL-1 by Kupffer cells in rats with hepatoma

!NTRODUCTIONKuPffer eells are residential macroPhages in the1 iver,which Play a eritieal role in the maintenaneeof normal liver function and in immunal surveilaneeof hePatoeellular earcinoma(HCC)and othereaneers〔l].The bio一ogieal immune modulants havebeen used for treating Patients with HCC and othereaneers[2〕.In our previous studies,the eombineduse of biological immune modulants showed bettereffeets.The normal rats and hePatoma rats indueedby DEN(Diethylnitrosamine)were treated …     

鼠肝老化进程中枯否细胞对肝细胞的影响及机制

目的研究肝脏老化时枯否细胞（ＫＣ）在肝细胞（ＨＣ）功能损害中的地位和机制．方法应用ＨＣＫＣ共同培养技术研究６，１２，１８和２４月龄大鼠（每组５只）ＫＣ对ＨＣ蛋白质合成和线粒体代谢水平的影响，并探讨了这种影响与老化ＫＣ分泌功能改变的关系．结果单独培养的２４月龄组ＨＣ蛋白质合成能力和线粒体代谢水平较６月龄组明显降低；各月龄组ＨＣ与６月龄组ＫＣ共同培养时，两指标较单独培养者均有明显增加，与２４月龄组ＫＣ共同培养时则显著降低．ＬＰＳ（１０ｎｇ／Ｌ）对单独培养的ＨＣ蛋白质合成和线粒体能量代谢无明显影响，但对共同培养系统中６月龄ＫＣ的增强作用和２４月龄ＫＣ的抑制作用具有明显的放大作用．２４月龄组ＫＣＴＮＦ、ＩＬ８、ＮＯ的分泌水平较６月龄组ＫＣ明显升高，ＰＧＥ２明显降低．各组ＫＣ受ＬＰＳ刺激后ＴＮＦ和ＮＯ水平较未刺激组均有明显升高，其增值以高月龄组为显著；６和１２月龄组ＫＣ受刺激后ＩＬ８水平明显升高，１８和２４月龄组无明显变化；ＰＧＥ２的变化规律与ＩＬ８相反．结论ＫＣ在鼠肝老化时ＨＣ受损过程中起重要作用，这可能与老化ＫＣ分泌细胞因子谱有改变，导致ＨＣ分子微生态环境变化有关．     

Difference between periportal and pericentral Kupffer cells in uptaking lipopolysaccharides in rats

ＤｉｆｅｒｅｎｃｅｂｅｔｗｅｅｎｐｅｒｉｐｏｒｔａｌａｎｄｐｅｒｉｃｅｎｔｒａｌＫｕｐｆｅｒｃｅｌｓｉｎｕｐｔａｋｉｎｇｌｉｐｏｐｏｌｙｓａｃｃｈａｒｉｄｅｓｉｎｒａｔｓＣＨＥＮＸｉａｎＭｉｎｇ１，ＬＩＵＪｉｎ＿Ｃｈｕｎ２，ＸＵＲｅｉＬｉｎｇ１，...     

Difference between periportal and pericentral Kupffer cells in lipopolysaccharide uptake in rats

AIM: To reveal the difference in the ability of Kupffer cells in the periportal and pericentral regions of the liver to uptake lipopolysaccharides (LPS) injected into the portal vein.METHODS: Male Wistar rats were divided into two groups: normal control group (n = 6) and GdCl₃-treated group (n = 8). Sixteen hours before the experiment, rats in the GdCl₃-treated group were injected with GdCl₃ via the tail vein to eliminate Kupffer cell function specifically in the periportal region. LPS at a dose of 20 μg/100 g body weight was injected into rats of both groups via the portal vein. Zero, 2, 5, 10, 30, and 60 min after LPS injection, liver samples were obtained and the distribution of LPS in Kupffer cells was observed by immunofluorescence imaging of monoclonal antibody-specific LPS staining using a confocal laser scanning microscope.RESULTS: In the normal control group, positive reactions to LPS were found in Kupffer cells in the periportal region with the peak at two minutes after LPS injection. Kupffer cells in the pericentral region showed the peak at five minutes after LPS injection, but its fluorescent intensity to LPS at the peak time in the cytoplasm was significantly lower than that of Kupffer cells in the pericentral region. In the GdCl₃-treated group, Kupffer cells in the pericentral region showed the peak at two minutes following LPS injection, and the LPS fluorescent intensity showed no significant difference from that of the normal control rats at the peak point. No significant changes of LPS fluorescent intensities were found in Kupffer cells in the periportal region at various time points following LPS injection in GdCl₃-treated rats.CONCLUSION: Kupffer cells in the periportal and pericentral regions showed differences in LPS uptake via the portal vein.     

干扰素α-2b联合利巴韦林治疗慢性丙型肝炎患者肝内免疫细胞的变化

目的观察干扰素α-2b和利巴韦林联合治疗前后漫性丙型肝炎患者肝内免疫细胞动态变化情况，为研究免疫调节疗法提供依据。方法利用流式细胞计数仪对42例慢性丙型肝炎患者应用联合治疗前及其中11例治疗后患者末梢血和（或）肝脏组织进行分析。结果与对照组相比慢性丙型肝炎组肝脏内CD56^＋、CD57^＋、CD161^＋细胞及CD56^＋T淋巴细胞阳性率明显减少（P〈0．01），CD161^＋T淋巴细胞有减少倾向；CD56^＋T淋巴细胞表达的CD28可见减少，CD152的表达可见增加（P〈0．05）；CD83^＋CD1a^＋细胞阳性率有减少倾向，CD80^＋CD11c^＋、CD86^＋CD11c^＋细胞阳性率明显减少（P〈0．01）；显效组减低的CD56^＋、CD161^＋、CD56T、CD161^＋T、CD80^＋CD11c^＋、CD86^＋CD11c^＋细胞治疗后可见增加。结论慢性丙型肝炎患者肝脏内自然杀伤细胞、自然杀伤T淋巴细胞数量及树突状细胞数量和功能减低，联合治疗使细胞免疫功能的抑制得到了改善。     

哺乳动物胃肠道D细胞形态和分布的实验研究

目的探讨Ｄ细胞，生长抑素免疫反应细胞（ＳＳＬＩ）在胃肠道包括阑尾在内的分布．方法应用免疫组化ＡＢＣ法，观察了猴（ｎ＝６），狗（ｎ＝１３）和小鼠（ｎ＝８）胃肠道ＳＳＬＩ细胞的分布．结果小鼠的胃窦和阑尾均有ＳＳＬＩ细胞，１３例狗的胃窦亦均有ＳＳＬＩ细胞，１３例狗的阑尾中１１例有ＳＳＬＩ细胞分布．小鼠的脾脏，狗、猴的胆囊未见ＳＳＬＩ细胞．结论ＳＳＬＩ细胞广泛分布于哺乳类动物胃肠道．小鼠和狗的阑尾粘膜层有ＳＳＬＩ细胞分布，提示阑尾具有内分泌功能．     

Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo.

PURPOSE: We investigated the effects of pegylated IFN-alpha2b (PEG-IFN-alpha2b) on the growth of human liver cancer cells. METHODS: The effect of PEG-IFN-alpha2b on the proliferation of 13 liver cancer cell lines was investigated in vitro. Chronological changes in growth and IFN-alpha receptor-2 (IFNAR-2) expression were monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with PEG-IFN-alpha2b. After HAK-1B cells were transplanted into nude mice, various doses of PEG-IFN-alpha2b or IFN-alpha2b were administered, and tumor volume, weight, histology, and IFNAR-2 expression were examined. RESULTS: PEG-IFN-alpha2b inhibited the growth of nine cell lines with apoptosis in a dose- and time-dependent manner. Continuous contact with PEG-IFN-alpha2b induced time-dependent growth inhibition and down-regulation of IFNAR-2 expression. PEG-IFN-alpha2b induced a dose-dependent decrease in tumor volume and weight, a significant increase of apoptotic cells, and a decrease in IFNAR-2 expression in the tumor. The clinical dose for chronic hepatitis C was also effective. The antitumor effect of PEG-IFN-alpha2b was significantly stronger than that of non-PEG-IFN-alpha2b in vivo. CONCLUSIONS: Continuous contact with PEG-IFN-alpha2b induces strong antitumor effects and the down-regulation of IFNAR-2 in HCC cells. The data suggest potential clinical application of PEG-IFN-alpha2b for the prevention and treatment of HCC.     

脂多糖诱导原代培养肝实质细胞与库普弗细胞表达和释放高迁移率族蛋白B1

目的观察LPS诱导HMGB1在肝实质细胞（HC）与库普弗细胞（KC）的表达和细胞外释放。方法培养瓶中分别培养原代HE和KC,24h后收获对照组和500μg/L LPS诱导组两种细胞,反复冻融,用半定量RT-PCR和Western blot法检测HMGB1 mRNA水平和HMGB1表达水平;接种原代HC和KC于24孔板中,继续培养6、12、24h和48h,Western blot法检测各时间点对照组和LPS诱导组培养液中HMGB1含量。结果LPS诱导24h后,与相应对照组比较,HC和KC中HMGB1 mRNA表达水平明显增强（t值分别为31.32和45.90,P值均〈0.05）,HMGB1表达水平也明显增强（t值分别为46.19和38.44,P值均〈0.05）;在6、12、24h和48h,对照组两种细胞及诱导组HC培养上清液中仅检测到少量HMGB1,延长培养时间,培养上清液中HMGB1含量无明显变化（F=1.61,P〉0.05）;与对照组比较,诱导组KC培养液中的HMGB1含量在6h无显著增加（t=1.48,P〉0.05）,但随培养时间延长,其含量明显增高（F=42.74,P〈0.05）,且在12、24h和48h均明显高于对照组（t值分别为21.95,32.39和44.16,P值均〈0.05）。结论LPS可诱导HC和KC中HMGB1表达增强,HC不主动释放HMGB1,而KC能主动释放HMGB1到细胞外。     

大肠癌患者血清sIL-2R和TNF检测的临床意义

目的研究大肠癌患者血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）和肿瘤坏死因子（ＴＮＦ）变化的临床意义．方法采用双抗体夹心ＥＬＩＳＡ法对７６例大肠癌患者手术前后血清ｓＩＬ－２Ｒ和ＴＮＦ水平进行检测，其中根治性手术４８例，姑息性手术２８例，以４０例献血员为正常对照组．结果大肠癌患者血清ｓＩＬ－２Ｒ（Ｕ／Ｌ）和ＴＮＦ（ｐｇ／Ｌ）分别为６０３６±９４３和９６２±９１，明显高于正常对照组的２０８３±７９６和２５１±４７（Ｐ＜００１），两者的增高与大肠癌Ｄｕｋｅ分期及手术方式不同密切相关．结论动态观察血清ｓＩＬ－２Ｒ和ＴＮＦ的变化，可作为大肠癌诊断、评价疗效及监测预后的参考指标．     

隆起糜烂性胃炎与胃黏膜G细胞、D细胞、壁细胞的相关性

[目的]观察隆起糜烂性胃炎（raised erosive gastritis,REG）脾胃湿热证、脾胃虚弱证及正常胃黏膜G细胞、D细胞、壁细胞数目以及G、D细胞数目比值（G/D）,研究三者之间上述指标的差异.[方法]选择REG中医辨证符合脾胃湿热证、脾胃虚弱证患者65例,并设正常对照组11例,所有受试者均空腹行胃镜检查,取胃窦大弯标本行快速尿素酶试验及组织染色法检测幽门螺杆菌（Hp）及G细胞、D细胞的免疫组织化学染色检测,取胃体大弯标本行苏木精-伊红染色检测壁细胞.[结果]REG组及其Hp阳性、阴性者的G、D细胞数目均较正常对照组有下降趋势,但差异均无统计学意义（P＞0.05）,G/D比值比较亦无统计学意义（P＞0.05）,而壁细胞数目均非常显著的低于正常对照组（均P＜0.01）;REG组Hp阳性与阴性者之间的G细胞、D细胞、壁细胞数目及G/D比值比较差异均无统计学意义（均P＞o.05）;脾胃湿热证组、脾胃虚弱证组较正常对照组的G细胞、D细胞数目有下降趋势,但差异均无统计学意义（均P＞0.05）,G/D比值比较无统计学意义（P＞0.05）,而壁细胞数目则均低于正常对照组（P＜0.05,P＜0.01）;脾胃湿热证组与脾胃虚弱证组G细胞、D细胞、壁细胞数目比较差异均无统计学意义（P＞0.05）,而脾胃湿热证组的G/D比值显著高于脾胃虚弱证组（P＜0.01）;脾胃湿热组、脾胃虚弱组Hp阳性与Hp阴性者G细胞、D细胞、壁细胞数目及G/D比值比较差异均无统计学意义（P＞0.05）.[结论]REG患者壁细胞数目较正常人低,脾胃湿热证者的G/D比值较脾胃虚弱证者高,针对REG可以尝试以保护胃黏膜为主进行治疗.     

Chaga mushroom (Inonotus obliquus) induces G0/G1 arrest and apoptosis in human hepatoma HepG2 cells

AIM: To investigate the anti-proliferative and apoptotic effects of Chaga mushroom (Inonotus obliquus) water extract on human hepatoma cell lines,HepG2 and Hep3B cells. METHODS: The cytotoxicity of Chaga extract was screened by 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological observation,flow cytometry analysis,Western blot were employed to elucidate the cytotoxic mechanism of Chaga extract. RESULTS: HepG2 cells were more sensitive to Chaga extract than Hep3B cells,as demonstrated by markedly reduced cell viability. Chaga extract inhibited the cell growth in a dose-dependent manner,which was accompanied with G0/G1-phase arrest and apoptotic cell death. In addition,G0/G1 arrest in the cell cycle was closely associated with down-regulation of p53,pRb,p27,cyclins D1,D2,E,cyclin-dependent kinase (Cdk) 2,Cdk4,and Cdk6 expression. CONCLUSION: Chaga mushroom may provide a new therapeutic option,as a potential anticancer agent,in the treatment of hepatoma.     

奥曲肽对重症急性胰腺炎大鼠枯否细胞m2极化功能的调节作用

目的探讨生长抑素类似物奥曲肽对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠枯否细胞(Kupffer cells)m2极化功能的调节作用。方法采用经胰管逆行注射5%牛黄胆酸钠和0.9%NaCl分别建立大鼠重症急性胰腺炎模型和对照组模型。36只SD大鼠随机分为六组:假手术组(S)、SAP组、奥曲肽治疗组(ST)、生理盐水治疗组(NT)、奥曲肽预防组(SP)、生理盐水预防组(NP),分别于造模后24 h处死,胶原酶Ⅳ体内灌注肝脏,采用25%、50%Percoll液密度梯度离心法提取肝Kupffer细胞。Elisa检测血清中TNF-ɑ、IL-4、IL-10水平,RT-PCR检测肝Kupffer细胞内极化水平,即TNF-ɑ、IL-4、IL-10的表达,HE染色观察胰腺组织病理损伤情况。结果 (1)SAP组、生理盐水治疗组和预防组血清中TNF-ɑ的水平明显升高,与奥曲肽治疗组相比差异显著(P<0.05或0.01),与奥曲肽预防组比较并无明显差异。奥曲肽治疗组和预防组IL-4水平明显增高,与其他组相比有显著差异(P<0.01),而其两组之间IL-4水平无差异。IL-10水平在奥曲肽治疗组明显升高,与SAP组、生理盐水治疗组和预防组相比差异显著(P<0.01),而IL-10水平在奥曲肽预防组并未见明显升高,与奥曲肽治疗组相比有明显差异(P<0.05)。(2)肝脏Kupffer细胞中,与假手术组相比,TNF-ɑ在SAP组的表达明显上升(P<0.01),而在奥曲肽治疗组和预防组的表达明显降低,与假手术组、SAP组比较差异显著(P<0.01)。IL-4的表达量在SAP组明显下降,与假手术组相比差异显著(P<0.01),而在奥曲肽治疗组和预防组的表达量明显上升,与SAP组、生理盐水治疗组和预防组相比差异显著(P<0.05或0.01)。SAP组与假手术组相比,IL-10的表达量显著降低(P<0.01),而其表达量在奥曲肽治疗组和预防组明显升高,与假手术组、SAP组、生理盐水治疗组和预防组相比差异明显(P<0.01或0.05)。(3)SAP组、生理盐水治疗组和预防组胰腺组织出血、水肿、坏死明显,奥曲肽治疗组和预防组胰腺组织炎症明显减轻。结论肝Kupffer细胞在SAP病情发展中起着重要作用,奥曲肽通过影响其中TNF-ɑ、IL-4和IL-10的表达和分泌,从而调节Kupffer细胞m2极化功能,对SAP具有一定的治疗作用。     

Effect of <Emphasis Type="Italic">gsp</Emphasis> oncogene on somatostatin receptor subtype 1 and 2 mRNA levels in GHRH-responsive GH3 cells

Growth hormone releasing hormone (GHRH) signals via G protein-coupled receptors (GHRH-R) to enhance intracellular Gαs/adenylyl cyclase/cAMP signaling, which in turn has positive effects on GH synthesis and release, as well as proliferation of the GH-producing cells of the anterior pituitary gland. Some GH-producing pituitary tumors express a constitutively active mutant form of Gαs (gsp oncogene). It has been reported that these tumors are more responsive to octreotide therapy. In this study we used a rat GH-producing cell line (GH3) stably transfected with the human GHRH-R cDNA (GH3-GHRHR cells) as a model to study the effects of gsp oncogene on somatostatin (SRIH) receptor subtype 1 and 2 (sst1 and sst2) mRNA levels. Transient transfection of gsp oncogene in GH3-GHRHR cells for 48 h increased intracellular cAMP levels and GH release. Phosphodiesterase (PDE) 4, sst1 and sst2 mRNA levels were increased by G protein mutation as assessed by real-time RT-PCR. Increased PDE mRNA levels in gsp-transfected cells may be a compensatory mechanism to the constitutive activation of cAMP-dependent pathway by G protein mutation and is consistent with reports of higher PDE expression in human pituitary tumor that express gsp. Our data suggest that higher expression of sst1 and sst2 mRNA induced by the gsp oncogene may be a mechanism by which gsp-positive tumors show a greater response to SRIH. GH3 cells permanently transfected with GHRH-R can be used for in vitro studies of actions of GHRH.     

胃肠道癌患者围手术期应用西咪替丁对NK细胞的影响

目的探讨西咪替丁（Cim）对胃肠道癌患者围手术期NK细胞的影响．方法胃肠道癌患者49例（胃癌6例，结肠癌3例，直肠癌16例）以围手术期是否应用Cim（400mg，3次／d，po，术前7d～10d；600mg，2次／d，iv，至术后d10）分治疗组和对照组.于入院时，手术前，术后d2，d10各抽取患者的外周血1次，动态检测NK细胞（鼠抗人CD57单克隆抗体）的变化．结果与常相比两组治疗前NK细胞数量均见降低．治疗组术后NK百分率即明显升高，至术后d10即达正常水平.对照组术后NK无明显升高，术后d10仍明显低于正常，差异有高度显著性（P＜0．01）治疗组入院时、手术前、术后d2，d10NK细胞的百分率（％）分别为14．60±3．91，15．640±3．41，17．40±3．28，20．68±4．13；对照组分别为14．88±2．76，13.17±2．43，14．50±2．77，15，67±2．55.结论围手术应用Cim有助于NK细胞恢复.这可能有利于降低局部复发和转移．     

The anterograde and retrograde infusion of glucagon antibodies suggests that A cells are vascularly perfused before D cells within the rat islet

Summary We have suggested that the order of cellular vascular perfusion within the islet is important in the regulation of islet hormone secretion. Anatomically, the A and D cells appear to be randomly dispersed throughout the mantle. Although islet capillary blood flow is known to be from the B-cell core to the A- and D-cell mantle, it has not yet been established whether the cells of the mantle may influence one another vascularly. Rat pancreata were perfused in vitro anterogradely and retrogradely with or without glucagon antibody in order to determine the order of cellular perfusion and interaction between the A and D cells in the islet mantle. Anterograde infusion of glucagon antibody did not affect insulin secretion, but rapidly decreased somatostatin secretion –46±8%, (p<0.005). Retrograde infusion of glucagon anti body decreased insulin secretion (–27±8%, p<0.005) but had no effect upon somatostatin secretion. This study not only confirms a core to mantle islet perfusion but also establishes that the A cell precedes the D cell in the terms of vascular perfusion. Thus within the islet, vascular borne insulin regulates the release of glucagon, which in turn, regulates the release of somatostatin. Somatostatin is vascularly neutral owing to its downstream position in the sequence (B to A to D) of cellular perfusion.     

Interferon γ modulates production of interleukin 1 and tumor necrosis factor by murine Kupffer cells

ABSTRACT— When mononuclear phagocytes, including Kupffer cells, are activated by various agents, they synthesize and release cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). In this study, we examined the effect of in vitro Kupffer cell activation by recombinant murine interferon γ (IFNγ) on IL-1 and TNF secretion. IFNγ enhanced TNF production in the presence or absence of lipopolysaccharide (LPS), but suppressed IL-1 production by Kupffer cells. Because IFNγ also stimulated prostaglandin E₂ (PGE₂) production, the effect of indomethacin, which is an inhibitor of cyclooxygenase and which inhibits PGE₂ biosynthesis, on IL-1 and TNF production by Kupffer cells was examined. As a result, indomethacin enhanced TNF production by Kupffer cells, but had no effect on IL-1 synthesis. These results suggested that IFNγ modulates the production of IL-1 and TNF by Kupffer cells through different mechanisms.     

Evaluation of the IL-2/IL-2R system in patients with liver cirrhosis or carcinoma

AIM: To evaluate the interleukin-2/interleukin-2 receptor (IL-2/IL-2R) system in patients with liver cirrhosis or carcinoma, and compare the immune function in those patients. The clinical significance of our results is also discussed. METHODS: Fifty patients with liver cirrhosis (LC), 50 patients with hepatocellular carcinoma (HCC), and 30 normal control subjects were studied. Cellular expression of the interleukin-2 receptor (mIL-2R) was examined by immunofluorescence, and the serum levels of IL-2 and soluble interleukin-2 receptor (sIL-2R) were measured by ELISA. RESULTS: The levels of IL-2 and mIL-2R expression in carcinoma patients were significantly lower than those in both patients with cirrhosis (P < 0.01) and control subjects (P < 0.01). The serum levels of IL-2 and the expression of mIL-2R in patients with cirrhosis were also lower than those in normal control subjects (P < 0.05). The serum levels of sIL-2R in carcinoma patients were significantly higher than those in both cirrhosis patients (P < 0.05) and control subjects (P < 0.01), and the sIL-2R levels in cirrhosis patients were higher than those in control subjects (P < 0.05). CONCLUSION: Patients with liver cirrhosis or carcinoma both have decreased immune function; however, this decrease is more pronounced in carcinoma patients. Such similarities in immune disturbances may be an important factor affecting the development of carcinoma in a cirrhotic liver.     

Superoxide and nitric oxide production by Kupffer cells in rats with obstructive jaundice: effect of internal and external drainage

BACKGROUND AND AIMS: The role of Kupffer cells in obstructive jaundice (OJ) has not been fully understood. The aims of the present study were to measure superoxide and nitric oxide (NO) production by Kupffer cells in experimental OJ in rats and to investigate the response to internal and external biliary drainage. METHODS: Eighty male Sprague-Dawley rats were assigned to four groups: sham operation, OJ, and internal and external biliary drainage. Kupffer cells were isolated on day 7 in the sham operation and OJ group, and on day 7 after drainage procedures. Cells were cultured with or without lipopolysaccharide (LPS). Superoxide production was quantified in cultured Kupffer cells at 2 h and 48 h, respectively, after cell isolation using the superoxide dismutase inhibitable ferricytochrome c reduction method. Nitrite production in cell culture supernatants was measured 48 h later using Greiss reagents. RESULTS: Without LPS stimulation, Kupffer cells produced comparable superoxide and nitrite in each group (P > 0.05). With LPS stimulation, Kupffer cells in the OJ group produced significantly higher superoxide anions than the other groups (P = 0.006). Nitrite production was significantly increased in the OJ group and external biliary drainage group compared to rats in the sham operation and internal drainage groups (P < 0.01). CONCLUSIONS: Kupffer cells from rats with OJ produce great amounts of endotoxin-mediated oxidants. Both internal and external biliary drainage can decrease the elevated superoxide production. Internal drainage is superior to external drainage for reversing the distortional capacity of NO production by Kupffer cells.