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1.
The effects of hyperbaric oxygen (HBO) on mouse skin two-stage chemical carcinogenesis were examined. Six-week-old inbred CD-1 female mice were divided into the following five groups: group 1, normoxia and application of 25 nmol 7,12-dimethylbenz[a]anthracene (DMBA) and 8.5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) (n=19); group 2, HBO and DMBA/TPA (n=21); group 3, HBO and DMBA/acetone (n=3); group 4, normoxia and acetone (n=3); and group 5, non-treatment group (n=5). HBO was started at the same time as DMBA. Mice were euthanized at 23 weeks after the start of the experiment. Mice in group 2 showed the occurrence of tumors at 8 weeks after the beginning of the experiment, while the occurrence of tumors in mice in group 1 was observed beginning at 9 weeks. There was a difference in occurrence among low-grade papillomas, high-grade papillomas and SCCs in both groups 1 and 2 by the χ2-test at end of the experiment (p<0.05). The Ki-67 labeling indices of tumors revealed that the percentages of positive cells in low-grade papillomas in groups 1 and 2 were 15.27 ± 2.54% and 29.67 ± 2.82%, respectively (p<0.01). The results suggested that the tumors in group 2, which was treated with HBO, were more progressive than those in group 1, which was not treated with HBO. In this study, HBO accelerated tumor cell proliferation and advanced tumor progression in skin carcinogenesis by DMBA/TPA.  相似文献   

2.
Sheep were subjected to immune challenge with either recombinant human interleukin-6 (rhIL-6; 2.0 μg/kg; n = 5), Escherichia coli lipopolysaccharide (LPS) endotoxin (400 ng/kg; n = 7), or saline (n = 6) to determine if IL-6 activates the febrile and hypothalamic-pituitary-adrenal axis (HPAA) responses in sheep, and to compare these responses with those associated with endotoxemia. Blood was collected over time to measure plasma adrenocorticotropic hormone (ACTH) and serum cortisol concentrations as indicators of HPAA activity. Unlike LPS, rhIL-6 was not pyrogenic in sheep at this challenge dose. In contrast, rhIL-6 elicited ACTH and cortisol responses that peaked earlier than those induced by LPS. These results suggest that this dose of IL-6, alone, is not sufficient to elicit the febrile response in sheep, however, it is a potent activator of the ovine HPAA response.  相似文献   

3.
Prostaglandin E2 (PGE2) and stromelysin are produced by equine chondrocytes and synovial cells in vitro in response to recombinant human (rh) interleukin-1 (IL-1) alpha and beta, and equine mononuclear cell supernatants (MCS) containing IL-1. However, culture conditions are important. PGE2 concentrations increase in proportion to the concentration of fetal calf serum (FCS) in the culture medium, whereas stromelysin concentrations are inversely proportional to the concentration of FCS. Equine MCS, containing a lower concentration of IL-1 than the concentration of rhIL-1 used in these experiments, stimulated production of much higher levels of PGE2 than rhIL-1. In addition, equine MCS induced the production of broadly similar levels of PGE2 by both chondrocytes and synovial cells, whereas rhIL-1 was more active on equine synovial cells than equine chondrocytes. Although equine MCS induced both stromelysin and PGE2 production by equine articular cells, on the whole rhIL-1 failed to induce stromelysin production. This supports previous observations of species restrictions in the activity of human IL-1 on equine cells. Therefore, experiments using mammalian cells and heterologous IL-1 should be interpreted with caution.  相似文献   

4.
Interleukin (IL)-10 exerts potent anti-inflammatory effects by suppression of both T-help (Th) 1 and Th2 cells. Previous studies have reported that IL-10 can ameliorate various inflammatory disorders. The present study was performed to examine whether IL-10 plasmid DNA could suppress development of atopic dermatitis (AD)-like skin lesions in NC/Nga mice, as an initial step towards the development of an appliance for use in dogs with AD. Intradermal injection of IL-10 plasmid DNA markedly inhibited the development of AD-like skin lesions, as evidenced by a marked decrease in skin symptoms and reduced inflammation within the skin lesions. Efficacy was confirmed by significant decreases in eosinophil ratio and serum IgE concentration, and a reduction in the number of Staphylococcus aureus recovered from the ear. Moreover, relative mRNA expression levels of IL-4 and interferon-γ in the skin lesions of mice injected with IL-10 plasmid DNA were also decreased compared with those of control mice. Of note, higher serum IL-10 levels in mice injected with IL-10 plasmid DNA were maintained compared with those in control mice. Taken together, the results indicate that IL-10 plasmid DNA can suppress the development of AD-like skin lesions by suppressing both Th1 and Th2 cell responses. Beneficial effects of IL-10 plasmid DNA may be expected in dogs with AD.  相似文献   

5.
Adult Naval Medical Research Institute (NMRI) mice, after prenatal exposure to retinoic acid (RA), were treated with a standard two-stage skin carcinogenesis regime to characterize hyperplastic epidermal foci that precede the appearance of cutaneous papillomas, and to investigate the in vivo long-term action of RA on adult mouse skin treated with DMBA (7,12 dimethyl benz[a]anthracene) and TPA (12-O-tetradecanoylphorbol 13-acetate). The results demonstrate that RA administered to pregnant mice had a long-term inhibitory action on the cell differentiation and development of hyperplastic lesions occurring prior to cancer on the adult skin of their offspring as well as a stimulatory effect on cell proliferation of these hyperplastic lesions.  相似文献   

6.
试验旨在探讨螺旋藻抗炎作用及其对机体免疫功能的影响。试验通过二甲苯致小鼠耳肿胀,构建小鼠体内炎症模型,以地塞米松为阳性对照药物,以小鼠耳肿胀为观察指标,探讨螺旋藻的体内抗炎作用;通过环磷酰胺构建小鼠免疫抑制模型,以不同剂量螺旋藻处理后测定免疫抑制小鼠及正常小鼠的脏器指数、血清白细胞介素2（IL-2）、白细胞介素6（IL-6）、白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）、干扰素γ（IFN-γ）水平,同时结合脾脏及胸腺病理组织学观察,探讨螺旋藻对免疫抑制小鼠及正常小鼠免疫功能的影响。结果表明,在螺旋藻对小鼠体内抗炎作用影响的试验中,0.3%螺旋藻灌胃对小鼠耳肿胀的抑制率极显著高于地塞米松对照组和其他螺旋藻处理组（P<0.01）,且螺旋藻对各试验组小鼠的脏器指数无不良影响,差异不显著（P>0.05）;在螺旋藻对小鼠免疫功能影响试验中,与空白对照组相比,环磷酰胺阳性对照组脾脏指数和胸腺指数极显著下降（P<0.01）;肝脏指数极显著上升（P<0.01）,其它各剂量螺旋藻处理组小鼠胸腺指数跟空白对照组相比差异不显著（P>0.05）,各组小鼠血清IL-2、IL-6、TNF-α、IFN-γ水平差异不显著（P>0.05）;通过病理组织学观察发现,环磷酰胺阳性对照组小鼠的脾小体萎缩、胸腺小体减少、淋巴细胞及网状细胞变性坏死,而各剂量螺旋藻处理组的脾小体和胸腺小体结构清晰完整、淋巴细胞增多。综上,螺旋藻能降低地塞米松和环磷酰胺对小鼠的免疫抑制,并且能修复小鼠脾脏和胸腺损伤,说明其在抗炎和缓解免疫抑制方面具有一定的作用。  相似文献   

7.
【目的】前期研究表明中药联合益生菌对致病性大肠杆菌所致小鼠腹泻具有明显的保护作用,本研究旨在进一步探讨中药联合益生菌对致病性大肠杆菌致小鼠腹泻的保护机制。【方法】选取小鼠60只,随机分为5组,空白组、模型组、中药组、益生菌组及中药联合益生菌组,每组12只。除空白组外,其余各组小鼠通过腹腔注射1×107CFU/kg大肠杆菌分离株菌悬液建立小鼠腹泻模型,空白组腹腔注射等量生理盐水。中药组灌胃给予中药液(2.5 g/kg蒲公英提取物、0.5 g/kg黄芪总黄酮及0.5 g/kg黄芪多糖),益生菌组灌胃给予枯草芽孢杆菌悬液(2×108CFU/kg),中药联合益生菌组灌胃给予中药液(2.5 g/kg蒲公英提取物、0.5 g/kg黄芪总黄酮及0.5 g/kg黄芪多糖)与枯草芽孢杆菌悬液(5×107CFU/kg)的混合液,1次/d,连续给药7 d。HE染色观察小肠组织病理学变化,扫描电镜观察小肠组织超微结构变化,ELISA法检测小鼠小肠匀浆和血清中肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)含量,RT-PCR法检测小肠组...  相似文献   

8.
Spleen cells from Toxoplasma lysate antigen (TLA)-sensitized BALB/c mice showed the strong cytotoxic activity against both natural killer (NK)-sensitive cells (YAC-1 and RL male-1) and NK-insensitive cells (P-815), when incubated with TLA or recombinant human IL-2 (rhIL-2). The increment of TLA concentration in culture medium increased the cytotoxic activity. Treatment of effector cells; spleen cells from TLA-sensitized mice incubated with TLA, with anti-asialo GM1 or anti-Thy-1 plus complement inhibited the cytotoxic activity of effector cells, whereas treatment with anti-mouse Lyt-2.2 serum plus complement had no effect on the cytotoxic activity. Treatment of spleen cells from TLA-sensitized mice with anti-asialo GM1 and/or anti-Thy-1 plus complement inhibited cytotoxic activities of effector cells. These results suggested that spleen cells sensitized with TLA both in vivo and in vitro were asialo GM1 positive and Thy-1 positive, and the majority of cytotoxic cells induced by TLA were similar to lymphokine-activated killer (LAK) cells induced by IL-2.  相似文献   

9.
Balb/c mice, injected i.p. with extracellular products (ECP) of Aeromonas salmonicida subsp. achromogenes (Asa), displayed symptoms similar to toxic shock syndrome. The LD(50) observed was between 1.5 and 2.0 microg g(-1) and the mice died within 19 h. Four inflammatory cytokines were measured in mice receiving sublethal ECP doses. TNF-alpha and IL-6 showed a sharp peak in the serum while IL-1 beta and IL-2 were not detected. When peritoneal macrophages were cultivated in the presence of ECP, AsaP1 (a toxic caseinolytic metallo-protease purified from ECP) or LPS, all cultures produced TNF-alpha, IL-6 and IL-1 beta. The same antigens were mitogenic in spleen cell cultures. Furthermore, IL-2 production, which is a normal T-cell response to ConA stimulation, was downregulated in spleen cell cultures from mice injected with ECP.  相似文献   

10.
There have been very few reports of experimentally induced animal models of allergic dermatitis, an immunologic disorder. This report describes the induction of histopathology confirmed allergic dermatitis in C57BL/6 mice along with the consistent clinical sign of alopecia following the administration of flea antigens emulsified in complete Freund's adjuvant (CFA). By comparing different strains of mice, routes of injection, types of adjuvants and different dosages of flea antigens, C57BL/6 mice were found to be most susceptible to flea antigens administered intramuscularly (i.m.) and subsequently developed dermatologic excoriations and local alopecia. The level of specific IgE reactive to flea antigens in C57BL/6 mice after the onset of clinical signs was significantly higher than such levels in mice without clinical signs, suggesting that flea antigen-specific IgE level can be correlated to the severity of allergic hyper-reaction. CD4(+) T lymphocytes and IL-4 rather than IL-10, or IFN-gamma were found to be the predominant cytokines associated with the clinical onset of allergic symptoms in C57BL/6 mice. Further, histopathologic analysis indicated that not only mast cells had infiltrated into the area of the skin lesion, but the damage was found to be at a stage where mast cells were degranulating causing considerable exacerbation of the local injury. In conclusion, this murine allergic dermatitis model induced by flea antigens may provide a useful means to evaluate vaccines or immunodulatory drugs; thus providing researchers with a tool to study allergy-related disorders and other parameters needed in the area of allergic investigations.  相似文献   

11.
Interleukin-16 (IL-16) is a proinflammatory cytokine produced by a variety of cells including lymphocytes, macrophages, mast cells, and eosinophils. We have shown in our previous studies increased expression of IL-16 mRNA and protein in caprine arthritis-encephalitis virus (CAEV)-infected goats blood. In this study, we determined the immunomodulatory effects of IL-16 in vitro using cells derived from CAEV infected and uninfected goats. Human recombinant IL-16 (rhIL-16) significantly increased chemotaxis of peripheral blood mononuclear cells (PBMCs) of both control and CAEV-infected goats. Pretreatment of PBMC with anti-goat CD4 monoclonal antibody inhibited IL-16-induced chemotaxis of PBMC of control and infected goats suggesting that IL-16 exerts its action in goats primarily by binding to CD4. The CAEV proviral DNA was less in caprine monocytes treated with rhIL-16 infected in vitro with CAEV. These data suggest inhibitory effect of IL-16 on viral integration. Flow cytometric studies indicated a trend toward IL-16-induced increased expression of lymphocyte activation markers. Combined with our previously reported data, these experiments suggest that increased IL-16 expression during CAEV infection may inhibit viral integration.  相似文献   

12.
试验旨在观察微囊化布拉迪酵母菌（Saccharomyces boulardii,S.boulardii）与微囊化粪肠球菌（Enterococcus faecium,E.faecalis）对小鼠溃疡性结肠炎（UC）的治疗效果并探讨其作用机制。采用3%葡聚糖硫酸钠（dextran sulfacte sodium,DSS）灌胃法制备小鼠UC动物模型,试验共分为6组,其中饮用DSS的小鼠随机分为5组：粪肠球菌菌粉组、微囊化粪肠球菌组、布拉迪酵母菌菌粉组和微囊化布拉迪酵母菌组给予不同的药物治疗,药物皆以溶液形式灌胃给药,UC模型小鼠（DSS组）每天饮用与药物等体积的生理盐水;正常对照组灌服与药物等体积的生理盐水。观察UC小鼠的症状和组织学变化,ELSIA检测血清中细胞因子（IL-6、IL-10与TNF-α）的含量,Western blotting检测小鼠结肠黏膜紧密连接蛋白（Occludin和Claudin-1）表达量。结果显示,与模型组相比,治疗后各益生菌组小鼠血清中TNF-α和IL-6含量均显著降低（P<0.05）,IL-10含量显著升高（P<0.05）,微囊化益生菌组小鼠髓过氧化物酶（MPO）活性及结肠损伤组织学评分（粪肠球菌粉组除外）均显著下降（P<0.05）,布拉迪酵母菌菌粉组与微囊化布拉迪酵母菌小鼠结肠黏膜内Occludin和Claudin-1表达量均显著升高（P<0.05）。粪肠球菌和布拉迪酵母菌可以缓解UC模型小鼠结肠炎症病变,且经过微囊化后的粪肠球菌和布拉迪酵母菌表现出更好的缓解小鼠急性溃疡性结肠炎病症效果,其机制与粪肠球菌和布拉迪酵母菌可以降低血清中IL-6与TNF-α含量,提高Occludin与Claudin-1的表达量密切相关。  相似文献   

13.
To understand roles of interleukin 6 (IL-6) family cytokines for pregnancy in mice, localization of IL-6 receptor (IL-6R) mRNA was investigated in non- and early pregnant uteri by in situ hybridization. IL-6R mRNA was expressed in all non-pregnant uteri and in pregnant uteri from the third day (Day 3) to the sixth day of pregnancy (Day 6; the day of plug = Day 1). IL-6R mRNA signals were detected in non-pregnant mice in the luminal and glandular epithelium. Signal strength varied according to the sexual cycle. There was no correlation between the signal strength of the IL-6R mRNA and the serum concentrations of progesterone and 17beta-estradiol, which show a monophasic rise in the non-pregnant sexual cycle. In pregnant mice, slight signals were detectable in the luminal and glandular epithelium on Day 3. IL-6R mRNA messages increased with progression towards Day 4, however, localization changed drastically on Day 5. Stromal cells abruptly expressed their mRNA on Day 5, and these cells strongly expressed it on Day 6. The function of IL-6R in the luminal and glandular epithelium might be different from that in the stroma during the implantation period. In addition, few signals were identified in the stromal cells adjacent to the luminal epithelium on Day 6. This suggests that there are two types of stromal cells on Day 6 in mice.  相似文献   

14.
This study was designed to develop a novel culture method for the efficient proliferation of canine peripheral blood lymphocytes (cPBL) for adoptive immunotherapy. When cPBL were cultured in the presence of concanavalin A (Con A), proliferation of cPBL was induced and expression of interleukin-2 receptor (IL-2R) which enables to respond to exogenously added IL-2 was upregulated. And then, when cPBL were cultured with recombinant human interleukin-2 (rhIL-2) in addition to Con A, proliferation was accelerated and increased to about 10-fold after 1 week. The phenotypic analysis showed that the main population of the cultured cPBL was consisted of CD8+ positive lymphocytes. Among them, CD4+CD8+ double positive (DP) lymphocytes had significantly increased, and the ratio of CD4+ single positive (SP) lymphocytes to CD8+ SP lymphocytes (CD4+SP/CD8+SP) was decreased as compared to before culturing. To evaluate the cytotoxic activity of cPBL cultured with Con A and rhIL-2, furthermore, cytotoxic assay was carried out against xenogeneic melanoma cell line (MeWo), which resulted in MHC-unrestricted cytokilling. These results suggest that the culture method of cPBL by the use of Con A and rhIL-2 may be useful for generating lymphokine activated killer cells, and also this may be beneficial for adoptive immunotherapy of tumor-bearing dogs.  相似文献   

15.
试验旨在观察丁酸梭菌-龙眼多糖发酵液预防给药对溃疡性结肠炎（ulcerative colitis，UC）模型小鼠的防治作用。30只SPF级雄性BALB/c小鼠随机分成空白组、模型组和发酵液组，10只/组。按10 mL/kg体重的剂量标准，空白组和模型组灌胃无菌去离子水，发酵液组灌胃丁酸梭菌-龙眼多糖发酵液，灌胃持续7 d。第8天开始，模型组和发酵液组连续7 d自由饮用5%葡聚糖硫酸钠（dextran sulfate sodium，DSS）溶液诱导UC模型，空白组自由饮用无菌水。试验第14天，称量所有小鼠体重，进行疾病活动指数（disease activity index，DAL）评分、临床评分，摘眼球采血后处死并解剖小鼠，取结肠肠段测量长度并进行组织学损伤评分，同时用甲醛固定后制作切片。ELISA检测血清中白细胞介素-6（interleukin-6，IL-6）、IL-10及肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）含量。结果表明，UC模型造模成功，模型组发病症状明显。与模型组相比，发酵液组小鼠体重下降程度显著降低（P<0.05），DAL评分、临床评分、结肠缩短程度及组织学损伤评分均极显著下降（P<0.01）。发酵液组小鼠结肠组织表现出相对完整的上皮层结构及隐窝，仅有部分炎症细胞侵入上皮组织。ELISA检测结果显示，发酵液组IL-6和TNF-α含量显著低于模型组（P<0.05），IL-10的含量显著高于模型组（P<0.05）。说明丁酸梭菌-龙眼多糖发酵液对DSS诱导的小鼠溃疡性结肠炎具有一定的防治作用，其作用机制可能与降低促炎因子IL-6和TNF-α含量、提升抗炎因子IL-10含量抑制炎症有关。  相似文献   

16.
The aim of the study was to observe the preventive and therapeutic effect of Clostridium butyricum-longan polysaccharide fermentation broth on mouse model with ulcerative colitis (UC).30 SPF male BALB/c mice were randomly divided into blank group,model group and fermentation broth group,10 mice/group.According to the dosage standard of 10 mL/kg body weight,sterile deionized water was administered to the blank group and model group,and Clostridium butyricum-longan polysaccharide fermentation liquid was administered to the fermentation broth group for 7 days.From the 8th day,the model group and the fermentation broth group were allowed to drink 5% dextran sulfate sodium (DSS) solution for 7 consecutive days to induce the UC model,and the blank group was free to drink sterile water.On the 14th day,all mice were weighed,and DAL scores and clinical scores were scored.Then the mice were dissected after eyeball collection and blood sampling.The length of the colon was measured and scored for histological damage of the colon,sections were made after formalin fixation.The content of IL-6,IL-10 and TNF-α in serum were detected by ELISA.The results showed that UC model was established successfully and symptoms were obvious in the model group.Compared with the model group,the weight loss of the mice in the fermentation broth group was significantly reduced (P<0.05),DAL score,clinical score,colon shortening degree and histological injury score were extremely significantly reduced (P<0.01).The colon tissue of mice in the fermentation broth group showed a relatively complete epithelial structure and crypts,and only part of the inflammatory cells invaded the epithelial tissue.ELISA results showed that the IL-6 and TNF-α levels in the model group were significantly higher than those in the fermentation broth group (P<0.05),and the IL-10 content was significantly lower than that in the fermentation broth group (P<0.05).It showed that Clostridium butyricum-longan polysaccharide fermentation broth had a certain preventive effect on DSS-induced UC in mice,and its mechanism might be related to reducing the content of IL-6 and TNF-α,increasing the content of IL-10,and inhibiting inflammation.  相似文献   

17.
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18.
The present work compared inbred (CBA/Ca) and outbred (Swiss white) strains of mice for their capacity to cope with a Neospora caninum infection and to consistently produce tissue cysts. In each experiment Swiss white and CBA/Ca mice were given three different doses of NC-1 tachyzoites. Lymphoproliferative and humoral responses as well as cytokine production were evaluated eight weeks after infection (PI) whereas tissue cyst production and histopathology were assessed 4, 6 and 10 weeks PI in immunosuppressed mice. Tissue cysts were observed 10 weeks after infection only in CBA/Ca mice receiving the two highest inoculum doses. Furthermore this strain showed the highest specific lymphoproliferative response. A mixed cytokine response with elevated IFN-gamma and fairly low IL-4 and IL-10 secretion was recorded. In both strains, no lesions were observed in the tissues of infected mice. This study indicates that CBA/Ca female mice infected with 5 x 10(6) NC-1 tachyzoites represent a useful model for the study of specific maternal immune responses in pregnant animals.  相似文献   

19.
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20.
The objective of the study was to determine the cellular and cytokine responses associated with dinitrofluorobenzene (DNFB)-induced skin contact hypersensitivity (SCH), as an indicator of cell-mediated immune response, in the chicken. The thickness of the DNFB-treated foot web was increased by 6h.p.i. (hours post-induction), peaked by 24h.p.i. and then declined gradually until the lowest measurements were observed at 72h.p.i. Infiltration of eosinophils was the highest at 6 and 12h.p.i. and gradually declined by 48h.p.i. The degree of infiltration of both CD8+ and CD4+ T cells varied with mild infiltration observed at 6h.p.i., moderate to heavy infiltration observed at 12h.p.i. that persisted through 24 and 48h.p.i. and declined by 72h.p.i. Infiltration of macrophages during the study period was prominent, yet less remarkable differences were recorded between observations. Expression of interleukin (IL)-4, IL-6, IL-10 and interferon (IFN)-gamma in skin tissue was at its highest at 6h.p.i. compared to other observed time points, yet only the expression of IFN-gamma and IL-10 genes turned out to be significantly higher at 6h.p.i. compared to all other time points. In conclusion, DNFB-induced SCH in chicken was associated with an early up-regulation of cytokine genes, and infiltration of eosinophils along with macrophages, CD8+, and CD4+ T cells at the site of induction.  相似文献   

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