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1.
本试验旨在研究和探讨抗类风湿性关节炎(rheumatoid arthritis,RA)药物花艽-6的抗炎作用及其抗炎机理。采用二甲苯致小鼠耳肿胀法、醋酸致小鼠毛细血管通透性增高法、甲醛和蛋清致小鼠足跖肿胀法,以及棉球致小鼠肉芽组织增生法分别研究了该药物的抗急性、亚急性和慢性炎症的作用。通过复制佐剂性关节炎(adjuvant arthritis,AA)大鼠模型研究花艽-6对其血清中IL-1β、IL-6和TNF-α含量的影响。花艽-6对小鼠二甲苯所致的耳肿胀、醋酸所致的腹腔毛细血管通透性增高、甲醛和蛋清所致的足跖肿胀和棉花所致的肉芽组织增生均具有显著或极显著的抑制作用。花艽-6具有抗炎作用,可显著降低AA大鼠血清中IL-1β、IL-6和TNF-α的表达,对RA具有治疗作用。  相似文献   

2.
Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) synergistically induce and sustain arthritis. Two competing hypotheses of arthritis induction are 1) that TNF preferentially mediates inflammation, whereas IL-1 impels bone destruction, or 2) that either cytokine controls the entire process. In this study, these propositions were tested in two experiments by instilling IL-1beta or TNF-alpha into one knee of Lewis rats (n = 6/group) to incite arthritis, after which semiquantitative scores for inflammation, bone resorption, osteoclasts, and cartilage integrity were acquired. In the induction study, IL-1beta or TNF-alpha (3, 10, or 30 micro g) was given once to incite arthritis. After 2 days, IL-1beta induced significant, dose-dependent increases in inflammation (mild to marked), bone resorption (minimal to moderate), and osteoclasts (minimal to moderate). In contrast, TNF-alpha induced minimal to mild inflammation but had little impact on resorption or osteoclasts. Both IL-1 and TNF (>/=10 micro g) yielded mild cartilage degeneration. Most lesion scores in TNF-treated rats were significantly lower than those in animals given the same dose of IL-1beta. In the persistence study, rats were injected once with IL-1 or TNF (10 micro g) and maintained for 2, 3, or 7 days. IL-1beta significantly enhanced inflammation (all 3 days), bone resorption (days 2 and 3), osteoclasts (days 2 and 3), and cartilage matrix loss (days 2 and 3), whereas TNF-alpha augmented inflammation (days 2 and 3) and cartilage degeneration (day 2) but not bone resorption or osteoclasts. Thus, both IL-1beta and TNF-alpha can launch inflammation, but IL-1beta drives skeletal destruction.  相似文献   

3.
Traditionally, adjuvants have been administered with antigens to enhance immunity. We studied the effect of several adjuvants such as Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA), lipopolysaccharide (LPS), homopolymers of polyinosinic-polycytidylic acid (poly I:C) and polyadenylic-polyuridylic acid (poly A:U), lithium chloride (LiCl), saponin Quil A and calcium phosphate gel (CaHPO(4)) on the immune response of mice to formalin-inactivated Mycoplasma agalactiae. The specific antibody or cytokine producing splenocytes were detected by ELISAspot and immunocytochemistry, respectively. Depending on the adjuvant given, the number of M. agalactiae-specific antibody producing cells was increased 2.5-6-fold. IgG was the major class of M. agalactiae-specific antibodies followed by IgM, IgA and IgE. Among IgG isotypes, FCA, FIA, Quil A and CaHPO(4) induced an IgG1 response with substantial increase of the IgG2a, IgG2b and IgG3 isotypes while poly I:C shifted the response toward an IgG2a/IgG3 production. Finally, poly A:U induced an IgG2b response while LPS and LiCl augmented the IgG3/IgG1/IgG2a secretion. FCA augmented IL-4, IL-5 and IL-10 production suggesting a strong Th2 response, while IFN-gamma and IL-12 remained low; poly I:C enhanced IFN-gamma, IL-12 and TNF-alpha eliciting a Th1 response; poly A:U resulted in a IL-10, IL-5, IL-6 and IL-12 secretion; and LPS enhanced the IL-10, IL-6 and TNF-alpha production. Our data show that adjuvants augment M. agalactiae-specific antibody production and lead to B cell isotype-switching via the appropriate cytokine milieu. Certain adjuvants, such as poly I:C, therefore, appear as promising immune enhancers for vaccination against M. agalactiae infections.  相似文献   

4.
In this study, several cytokine responses were investigated during Mycoplasma hyopneumoniae (Mhp) infection using a gnotobiotic infection model. We found that several inflammatory cytokines (IL-1beta, IL-8, IL-18, and TNF-alpha) and an anti-inflammatory cytokine IL-10 were induced from peripheral blood mononuclear cells (PBMC) of germ-free (GF) piglets stimulated with heat killed Mhp whole antigens, but no IFN-gamma and IL-4 were induced by Mhp. After the intranasal infection of Mhp, IL-1beta, IL-8, IL-18, and IFN-gamma were also detected in the broncho-alveolar lavage fluids (BALF). The antigen-specific IFN-gamma and IL-10 responses after infection of Mhp were gradually suppressed during Mhp infection as well as non-specific immune response to concanavalin A (ConA) and lipopolysacchalide (LPS) at early stage of infection. These results suggested that Mhp infection modulates the immune response of pigs by inducing several cytokines, and causes immuno-suppression of pigs in a gnotobiotic condition.  相似文献   

5.
Canine rheumatoid arthritis and inflammatory cytokines.   总被引：5，自引：0，他引：5  
Bioassays were developed to detect canine pro-inflammatory cytokines. These enabled characterisation of these cytokines and their isoforms and provided means for their assay in the joints of dogs with different naturally occurring arthropathies. Canine IL-1 was detected by its induction of proliferation of D10(N4)M cell line, whilst IL-6 had a proliferative effect on B9 cell line. TNFalpha had a cytotoxic effect on WEHI 164 (13) cells. Partial purification of the cytokines was achieved by FPLC ion-exchange chromatography and two isoforms of IL-1 were shown, possibly corresponding to IL-1alpha and IL-1beta. TNFalpha only appeared as one isoform whereas IL-6 showed at least five isoforms, possibly corresponding to the other molecules in the IL-6 family, such as IL-11 and oncostatin M. Analysis of synovial fluids from dogs with osteoarthritis (OA) and rheumatoid arthritis (RA) showed that IL-1 and TNFalpha bioactivity was not readily detectable at increased levels in diseased joints but that IL-6 was significantly increased in both diseases. It is now important to determine the role of IL-6 in OA and RA in the dog, particularly in the induction of proteolytic enzymes which lead to cartilage loss.  相似文献   

6.
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7.
OBJECTIVE: To evaluate proinflammatory effects of the second-generation synthetic lipid A analogue E5564 on equine whole blood and isolated monocytes and to determine the ability of E5564 to prevent LPS (lipopolysaccharide)-induced procoagulant activity (PCA); tumor necrosis factor (TNF)-alpha production; and mRNA expression of TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-10 by equine monocytes. SAMPLE POPULATION: Venous blood samples obtained from 19 healthy horses. PROCEDURES: Whole blood and monocytes were incubated with Escherichia coli O111:B4 LPS, E5564, or E5564 plus E coli O111:B4 LPS. Whole blood and cell supernatants were assayed for TNF-alpha, and cell lysates were assayed to determine PCA. Expression of mRNA for TNF-alpha, IL-1beta, IL-6, and IL-10 by monocytes was determined by use of real-time quantitative PCR assay. RESULTS: Minimal proinflammatory effects were detected in whole blood and monocytes. In addition, E5564 inhibited LPS-induced PCA and TNF-alpha production in a concentration-dependent manner. Furthermore, E5564 significantly inhibited LPS-induced mRNA expression of TNF-alpha, IL-1beta, and IL-10 and decreased LPS-induced expression of IL-6. CONCLUSIONS AND CLINICAL RELEVANCE: The second-generation synthetic lipid A analogue E5564 lacked agonist activity in equine whole blood and monocytes and was a potent antagonist of enteric LPS. Therefore, E5564 appeared to be the first lipid A analogue that has potential as an effective therapeutic agent in horses with endotoxemia.  相似文献   

8.
Opioids are useful and potent drugs for the management of pain in small animal patients. They have a wide therapeutic index and can be given by a number of different routes. Some of these techniques (e.g., epidural and intraarticular) allow for the production of profound analgesia in a localized area of the body while limiting the dose and the side effects, and others provide a noninvasive method for the delivery of continuous analgesia (e.g., transdermal administration).  相似文献   

9.
The requirement for IFN-gamma and/or TNF-alpha as co-stimulants with Babesia bovis merozoites for nitric oxide (NO) production was examined, as well as the regulatory role of IL-4 and IL-10. Purified B. bovis merozoites did not induce the production of NO in undifferentiated monocytes without addition of exogenous IFN-gamma and TNF-alpha unless the monocytes taken ex vivo were producing TNF-alpha endogenously. Under the latter condition, the NO production resulting from merozoite stimulation remained IFN-gamma-dependent. There was no evidence for endogenous synthesis of TNF-alpha in monocyte-derived macrophages (MDM), and merozoites alone were incapable of inducing TNF-alpha mRNA in MDM. However, while merozoites plus IFN-gamma induced TNF-alpha mRNA expression in MDM, NO was not produced. Both IL-4 and IL-10 inhibited expression of iNOS and production of NO in merozoite-stimulated monocytes.  相似文献   

10.
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11.
探讨佐剂性关节炎(AA)大鼠成纤维样滑膜细胞(FLS)的体外培养及鉴定方法,制备AA大鼠模型,采用组织块培养法培养AA大鼠FLS,并通过形态学、透射电镜及RT-PCR方法对FLS进行鉴定.结果表明,培养的滑膜细胞具有成纤维细胞的形态和特征,呈长梭形板向生长,RT-PCR方法检测波形蛋白表达较高.本研究成功地培养出了AA...  相似文献   

12.
Trans-resveratrol is a biologically active compound present in certain foods that has anti-inflammatory and anticancer properties. These beneficial effects are derived from both the immune system and cytokines. The purpose of this study was to determine the immunomodulatory effect of trans-resveratrol on the ex vivo production of inflammatory and anti-inflammatory cytokines stimulated by lipopolysaccharides (LPS). Trans-resveratrol (0, 0.01, 0.1, 1, and 10 microM) was added to blood samples from male Sprague-Dawley rats (n = 6) along with 100 U of LPS (Escherichia coli serotype, 055B5). The samples were then incubated for 4 h at 37 degrees C and centrifuged. Finally, concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the plasma were analyzed using an enzyme-linked immunosorbent assay (ELISA). The production of inflammatory (TNF-alpha and IL-1beta) and anti-inflammatory (IL-6) cytokines was suppressed by trans-resveratrol in a concentration-dependent manner. These results support the hypothesis that the immunomodulatory effect of trans-resveratrol plays an important role in disease conditions that involve an overproduction of inflammatory cytokines.  相似文献   

13.
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14.
Epsilon-polylysine micro particles (SGEPL) and polyethyleneimine micro particles (SGPEI) were developed by the addition of a hydrophobic group and the immunological characterization of these micro particles and aluminum hydroxide (ALUM) was investigated. BALB/c mice were injected intraperitoneally with ovalbumin (OVA) as an antigen and SGEPL, SGPEI or ALUM as an adjuvant. The results showed that the mice injected with SGEPL produced a significant portion of anti-OVA antibody subclass IgG2a in the sera and suppressed interleukin (IL)-4 and IL-5, but enhanced IL-12 and interferon-gamma (IFN-gamma) from the spleen cells. Similar results relating to cytokines were also obtained, even without OVA. Direct stimulation with SGEPL to na?ve BALB/c mouse spleen cells induced IL-12 and IFN-gamma. Both spleen and purified B cells produced IgG1 and IgE after stimulation with IL-4 and the anti-CD40 monoclonal antibody. With the addition of SGEPL, the IgE production from the cells was suppressed as a result of enhanced IFN-gamma production. Furthermore, IgE production was also suppressed in the purified B cells without the influence of IFN-gamma or IL-12. Thus, we suggest SGEPL drives cytokine production to Th1 profile. It will be a novel promising adjuvant based on this viewpoint.  相似文献   

15.
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16.
This study was conducted to analyze cytokine production mechanisms in mice after Bartonella henselae stimulation. BALB/c mice were inoculated intraperitoneally with 3 x 10(6) colony forming units of B. henselae (Houston-1 strain) twice at 10-day interval. Spleen cells were harvested from the mice and stimulated with the organisms. Following the stimulation, interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), IL-10, IL-12 and tumor necrosis factor-alpha (TNF-alpha) were measured in the culture supernatants of the spleen cells by ELISA. The spleen cells specifically secreted IFN-gamma, but not IL-4, indicating that T helper 1 (Th1) cells were activated following B. henselae stimulation. In addition, IL-10 and TNF-alpha productions were also detected in the culture supernatants of spleen cells. Neutralization of IL-10 in the culture supernatants significantly enhanced the production of IFN-gamma from the spleen cells stimulated with B. henselae. These results indicate that B. henselae predominantly stimulated Th1 cells and resulted in secreting IFN-gamma, however the production was partially inhibited by IL-10, which was produced simultaneously.  相似文献   

17.
Maternal cytokines may play instructive roles in development of the neonatal immune system. However, cytokines in colostrum and milk and their transfer from mothers to neonates have not been well documented, except for TGF-beta. Swine provide a unique model to study lactogenic cytokines because the sow's impermeable placenta prohibits transplacental passage. We investigated IL-6 and TNF-alpha (pro-inflammatory), IFN-gamma and IL-12 (Th1), IL-10 and IL-4 (Th2) and TGF-beta1 (Th3) concentrations in sow serum and colostrum/milk and serum of their suckling and weaned piglets and in age-matched colostrum-deprived gnotobiotic piglets. All cytokines were detected in colostrum/milk and correlated with concentrations in sow serum except for mammary-derived TNF-alpha and TGF-beta1. Detection of IL-12 and TGF-beta1 in pre-suckling and colostrum-deprived gnotobiotic piglet serum suggests constitutive production: other cytokines were undetectable confirming absence of transplacental transfer. Peak median cytokine concentrations in suckling piglet serum occurred at post-partum days 1-2 (IL-4>IL-6>IFN-gamma>IL-10). The effects in vitro of physiologically relevant concentrations of the two predominant lactogenic cytokines (TGF-beta1 and IL-4) on porcine naive B cell responses to lipopolysaccharide (LPS) and rotavirus (RV) were investigated. High (10 ng/ml) TGF-beta1 suppressed immunoglobulin secreting cell responses to LPS and rotavirus; low concentrations (0.1 ng/ml) promoted isotype switching to IgA antibody. Interleukin-4 induced inverse dose-dependent (0.1 ng>10 ng/ml) isotype switching to IgA and enhanced IgM secreting cell responses to LPS and rotavirus. In summary, we documented the transfer and persistence of maternal cytokines from colostrum/milk to neonates and their potential role in Th-2 biased IgA responses and reduced immunologic responsiveness of neonates.  相似文献   

18.
The objective of this study was to determine the effect of a nonionic silver nanocolloid administered orally for 7 or 14 days at three concentration levels (25 ppm, 2.5 ppm, and 0.25 ppm) on the phagocytic activity and mitogenic response of splenocytes and selected cytokine serum levels (IL-1beta, IL-6, IL-10, IL-12 p70, TNF-alpha) in NMRI mice at the early stage of experimental endotoxemia induced with single 30 microg/mouse dose of bacterial LPS. Regardless of the period of administration, silver nanoparticles enhanced the production of proinflammatory cytokines and anti-inflammatory cytokine IL-10, and they inhibited IL-12 p70 levels in response to LPS challenge. The studied nanoparticles' effect on splenocyte activity was determined by the period of administration. After 7 days of use, silver nanoparticles enhanced the phagocytic activity, and doses of 2.5 ppm stimulated the mitogenic response of splenocytes. After 14 days of administration, silver nanoparticles lowered the phagocytic activity regardless of the dose applied. Although the results obtained are ambiguous, they suggest that silver nanoparticles administered via the alimentary tract are more likely to increase an inflammatory response of an organism than offer protection after LPS challenge.  相似文献   

19.
The in vitro effect and the in vivo influence of recombinant swine IL-4 (rSwIL-4) were characterized in various swine cells and in nursery pigs on LPS-induced endotoxic shock and pro-inflammatory cytokine productions. In in vitro experiment, the rSwIL-4 induced a proliferation of CD4 positive T cells in mitogen-prestimulated peripheral blood mononuclear cell (PBMC). In addition, the rSwIL-4, which was produced from insect cells, promoted the differentiation of monocytes into immature dendritic cells in combination with granulocyte macrophage-colony stimulating factor (GM-CSF). Furthermore, the rSwIL-4 successfully suppressed the LPS-induced secretion of TNF-alpha, IL-1alpha, IL-6, IL-8, and IL-18 from swine alveolar macrophages when rSwIL-4 was treated at the same time with LPS. In in vivo experiment in nursery pigs, subcutaneous pretreatment of rSwIL-4, which was produced from baculovirus expression system, enhanced the severity of respiratory failure with endotoxic shock, and increased the production of TNF-alpha and IL-18 in response to inoculation with LPS. These results indicate that the rSwIL-4 is biologically active in both in vitro and in vivo treatments. Depending on the administration time, pro-inflammatory cytokine productions by IL-4 can cause either inhibitory or stimulatory regulation.  相似文献   

20.
Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) prevent development of T-helper type 2 (Th2) immune response and reverse established allergic responses in mouse models. However, little work on immune responses in piglets has been conducted in vivo. In this report, the ability of a porcine-specific CpG ODN to act as an immunostimulant and enhance immune responses of piglets to swine Pasteurella multocida living vaccine (SPML vaccine) was determined. The titre of IgG and IgG1/IgG2 isotype to SPML vaccine in serum, the proliferation of lymphocytes, SPML-specific interferon-gamma (IFN-gamma) and IL-6, TNF-alpha, IL-4 production of PBMCs in vitro and IFN-gamma, IL-6, TNF-alpha, IL-4, IL-10 in piglets serum were examined to identify the immune responses of the piglets. Immune responses of the piglets vaccinated with SPML and CpG ODN were significantly stronger than responses of piglets vaccinated with SPML alone. All these data summarized that immunostimulatory CpG ODN could modulate the immune response towards a Th1-like response when co-administered to piglets during SPML vaccination, which suggested that the therapeutic uses envisioned for these ODNs (as vaccine adjuvants and immunoprotective agents) may be applicable to husbandry animals.  相似文献   

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