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The early cytokines interferon-alpha (IFN-alpha), tumour necrosis factor-alpha (TNF-alpha), interleukin-1, -6 and -8 (IL-1, -6, -8) are produced during the most early stage of an infection. The activities of these cytokines have been studied extensively in vitro and in rodents, but in vivo studies on the role of these cytokines in infectious diseases of food animals are few. This review concentrates on in vivo studies of cytokine involvement in infectious respiratory diseases of swine, with an emphasis on viral infections. First evidence for the role of early cytokines in pneumonia in swine came from experimental infections with Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. The role of TNF-alpha and IL-1 in the symptoms and pathology of porcine pleuropneumonia has recently been proven by use of an adenovirus vector expressing the anti-inflammatory IL-10. In the authors' laboratory, studies were undertaken to investigate the relationship between viral respiratory disease and bioactive lung lavage levels of IFN-alpha, TNF-alpha, IL-1 and IL-6. Out of three respiratory viruses-porcine respiratory coronavirus (PRCV), porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV)-only SIV induced acute respiratory disease and severe lung damage by itself. Disease and lung pathology were tightly associated with the simultaneous production of IFN-alpha, TNF-alpha, IL-1 and IL-6. In challenge studies of SIV-vaccinated pigs, levels of IFN-alpha, TNF-alpha and IL-6, but not IL-1 were correlated with clinical and virological protection. Multifactorial respiratory disease was reproduced by combined inoculations with PRCV or PRRSV followed by LPS from Escherichia coli. In comparison with the respective single inoculations, which were subclinical, there was a true potentiation of disease and production of TNF-alpha, IL-1 and IL-6. TNF-alpha and IL-6 were best correlated with disease. In further studies, we will use more specific strategies to dissect the role of cytokines during viral infections.  相似文献   

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Colostrum contains factors that are protective for the neonate and may be a source of immunomodulary molecules that positively influence the immune status of the neonate. To confirm that colostrum contains a variety of cytokines with immunomodulatory properties, we established a bovine cytokine specific ELISA and five cytokines (IL-1 beta, IL-6, TNF-alpha, INF-gamma or IL-1 receptor antagonist, IL-1ra) in the whey samples from cows at different stages of lactation were monitored. The expression of cytokine mRNAs (IL-1 beta, IL-6, TNF-alpha and INF-gamma) in the colostral cells was detected by RT-PCR. The concentrations of cytokines in colostrum were significantly higher concentrations than those in the mature milk. A positive correlation was observed between the concentrations of IL-1ra and IL-1 beta in the colostrum samples. In conclusion, colostrum contains high levels of cytokines that could be produced and secreted in the mammary gland and that may have an immunomodulatory activity and influence neonatal immunity.  相似文献   

5.
This study was carried out to evaluate the effects of induced urolithiasis by high dietary calcium (Ca) or protein levels on biochemical analyte levels, redox status, selected inflammatory cytokines and histopathology in chickens. A total of 90 one-day-old white Hy-Line chicks were fed basal control diets containing 20% crude protein (CP) and 1% Ca until they reached 44 days of age. After that, the birds were divided into three groups (30 birds per group). All management factors (light, temperature, ventilation, stock density and diet) were identical among the three groups throughout the study except for the dietary Ca and protein percentages. Group I was fed a control diet containing 20% CP and 1% Ca, group II was fed a high-Ca diet containing 5% Ca, and group III was fed a high-protein diet containing 25% CP. Our findings clearly demonstrated that dietary imbalance (caused by high-Ca or high-CP levels) per se in chickens was physiologically harmful, as it was accompanied by post-mortem lesions; biochemical, redox status and histopathological alterations; and upregulation of inflammatory cytokines (interleukin (IL)-1β and IL-6). In particular, the birds fed the high-Ca diet clearly exhibited the most obvious alterations in most of the endpoints. In conclusion, this study constitutes the first extensive investigation of the effects of high-Ca or high-protein diets induced urolithiasis on growth performance, redox status, inflammatory cytokine levels and pathological characterization in chickens.  相似文献   

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The aim of the present study was to estimate the absorption of 125I-labeled proinflammatory cytokines--interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) from inflamed porcine uterus into the uterine venous blood. Moreover, in order to test the hypothesis that the above cytokines penetrate directly into ovaries and oviduct via local destination transfer in the area of the ovarian vascular pedicle and bypassing the systemic circulation, the concentration of IL-1beta, IL-6 and TNF-alpha in ovarian and oviductal tissues was also studied. These cytokine concentrations were also estimated in the ovarian venous blood. IL-1beta, IL-6 and TNF-alpha from both control and inflamed uteri were absorbed into the uterine venous blood, but it was higher (P < 0.05-0.001) from the pathologically changed uteri. The uterine tissues, particularly the endometrium, of both control and inflamed uteri retained all studied cytokines, but to a higher degree (P < 0.001) in the inflamed uteri. Injections of IL-1beta, IL-6 and TNF-alpha into the control and inflammatory changed uteri produced the presence of these proteins in the ovary and oviduct. However, the concentrations of IL-1beta and IL-6 in the ovarian and oviductal tissues was low after injections of control and inflamed uteri with these cytokines. In turn, administration of TNF-alpha into the inflammatory changed uteri lead to an enhancement in the concentration of this cytokine in the ovarian parenchyma (P < 0.05) and oviduct (P < 0.001). All studied cytokines were found in the ovarian venous blood after their injection into both control and inflamed uteri, which indicated its local destination transfer to the ovary. However, the concentration of cytokines increased (P <0.05-0.001) in the gilts with pathologically changed uteri as compared to controls. The study showed that both control and inflamed porcine uteri absorbed IL-1beta, IL-6 and TNF-alpha into the uterine venous blood, but the values of absorbed cytokines from inflamed uteri were higher. Moreover, the quantity and the manner of the studied cytokineS absorption into the uterine venous blood differed.  相似文献   

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The effects of N-acetylcysteine (NAC) on the pharmacokinetic parameters of acetaminophen (AP) in adult female beagles were studied. Each of eight dogs received a single i.v. injection of 150 mg/kg of AP as a 5% solution in a vehicle of 40% aqueous propylene glycol at 0 h. Each of four AP-treated dogs (Group I) received an oral dose of 140 mg/kg NAC as a 20% aqueous solution at 0 h, and 70 mg/kg at 30 min and 1 h post-AP administration. Four dogs (Group II) served as controls and received isotonic saline orally. Mild signs of AP toxicosis seen in both groups within 2-3 h of AP administration including depression, weakness, recumbency and methaemoglobinaemia. Relative to Group II, treatment with NAC (Group I) enhanced the elimination of AP from the body as indicated by the decreased plasma half-life (t1/2 = 1.06 h for Group I v. 1.78 h for Group II) and a higher elimination rate constant (beta = 0.67/h for Group I v. 0.40/h for Group II). Changes in the area under plasma concentration curve data (AUC = 0.39 mg.h/ml for Group I v. 0.65 mg.h/ml for Group II) were associated with a 61% increase in total body clearance of AP in Group I. The apparent volume of drug distribution Vdarea was not affected.  相似文献   

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The expression of mRNAs for the Toll-like receptors (TLRs) TLR2 and TLR4, pro- and anti inflammatory cytokines and their receptors was evaluated in mammary gland biopsy material collected from sows intramammarily inoculated with Escherichia coli strain O127 at parturition. Quantitative real-time RT-PCR analysis showed increased mRNA levels for TLR2, the proinflammatory cytokines interleukin IL-1beta and tumor necrosis factor-alpha TNF-alpha, and the anti-inflammatory cytokine IL-10 in the inoculated mammary glands 24h after inoculation. Increased mRNA levels of the proinflammatory cytokine IL-6 were only observed in the inoculated mammary glands of sows that developed clinical signs of mastitis. In contrast, the expression of the anti-inflammatory cytokine, transforming growth factor-beta 1 (TGF-beta1) mRNA was unaltered, as was mRNA expression for the IL-1 receptor type I (IL-1R1). Furthermore, IL-1beta and IL-10 mRNA expression was higher in the inoculated mammary glands of sows that developed clinical signs of mastitis compared with sows that remained clinically healthy. Notably, sows that developed clinical signs of mastitis had significantly lower pre-inoculation levels of IL-1beta mRNA than sows that remained clinically healthy. These findings suggest that development of coliform mastitis is associated with the level of local expression of regulatory cytokines in response to intramammary E. coli inoculation and infection.  相似文献   

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The objective of this study was to determine the effect of infection with Strongylus vulgaris on serum cytokines and plasma nitric oxide (NO) concentrations in helminth-naive ponies. Group 1 (n = 21) was given 500 S. vulgaris L3 larvae and group 2 (n = 7) received a saline control. Ponies were monitored daily for clinical signs, and blood was collected for complete blood cell counts and serum cytokines (TNF, IL-1, IL-6) quantification. Group 1 ponies were depressed, anorexic, and febrile for variable periods of time. Plasma NO was increased on day 21 in group 1 and on days 9 and 21 in group 2. Significant increases in total white blood cell counts, fibrinogen, and plasma protein concentrations in group 1 were found. Significant decreases in red blood cell counts and packed cell volume were also noted in group 1. There were no differences in serum cytokines across time in either group of ponies. Despite the lack of proinflammatory cytokine induction with the apparent inflammatory response to S. vulgaris there is evidence of a potential role of NO.  相似文献   

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We cloned, sequenced and analyzed the cDNAs encoding Camelidae inflammatory cytokines, including llama (lama glama) interleukin (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha and camel (Camelus bactrianus) IL-6 and TNF-alpha. The similarity levels of the deduced amino acid sequences of IL-1alpha, IL-1beta, IL-6 and TNF-alpha from llama (camel) to those from other mammalian species, ranged from 60.7% to 87.7%, 52.8% to 75.3%, 41.4% to 98.6%, and 72.9% to 99.6%, respectively. Phylogenetic analyses based on nucleic acid sequences showed that llama IL-1alpha, IL-1beta, IL-6 and TNF-alpha were more closely related to those of camel, pig, cattle, sheep and horse than to those of human, dog, cat, mouse and rat.  相似文献   

12.
The expression of mRNA encoding tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), IL-6 and IL-8 was studied, by in situ hybridization with a non-radioactive digoxigenin-labelled probe, in formalin-fixed, paraffin wax-embedded colonic tissue from pigs naturally infected with Salmonella typhimurium and S. choleraesuis. By in situ hybridization, a distinct positive signal for TNF-alpha, IL-1, IL-6 and IL-8 was detected in colon from all 12 infected pigs. Hybridization signals for all four inflammatory cytokines were detected primarily inflammatory cells infiltrating the lamina propria and submucosa. In comparison, expression of all four inflammatory cytokines was minimal in non-lesional colon of infected pigs and in normal colon from control pigs. The results suggest that these cytokines play an important role in the pathophysiological processes in porcine salmonellosis.  相似文献   

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OBJECTIVE: To determine the effects of intestinal ischemia and reperfusion on the expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mRNAs in the jejunum, liver, and lungs of dogs. ANIMALS: 8 healthy adult Beagles. PROCEDURES: In each dog, the cranial mesenteric artery was occluded for 0 (control group; n=4) or 60 (I-R group; 4) minutes, followed by reperfusion for 480 minutes; serum TNF-alpha and IL-6 activities and expression levels of TNF-alpha and IL-6 mRNAs in jejunal, hepatic, and lung tissues were measured before and at the end of the ischemic period and at intervals during reperfusion. For each variable, values were compared between the control and I-R groups at each time point. RESULTS: Compared with the control group, serum IL-6 activity increased significantly after 180 minutes of reperfusion in the I-R group; also, jejunal TNF-alpha mRNA expression increased significantly after 60 (peak) and 180 minutes of reperfusion. In the I-R group, expressions of IL-6 mRNA in the liver and TNF-alpha and IL-6 mRNAs in the lungs increased significantly at 480 minutes of reperfusion, compared with the control group. Serum TNF-alpha activity, expression of IL-6 mRNA in the jejunum, and expression of TNF-alpha mRNA in the liver in the control and I-R groups did not differ. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the liver, lungs, and jejunum contributed to the production of TNF-alpha and IL-6 after intestinal ischemia and reperfusion in dogs, suggesting that intestinal ischemia and reperfusion induce a systemic proinflammatory cytokine response in dogs.  相似文献   

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Johne's disease is characterized by a chronic enteritis that results in granulomatous inflammation, cachexia, and eventual death of cattle infected with Mycobacterium paratuberculosis. The cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) have been associated with granuloma formation and wasting in other disease syndromes. The potential role of these cytokines in the development and progression of Johne's disease has not been investigated. Using the polymerase chain reaction (PCR) and specific bovine oligonucleotide cytokine primers and probes, we examined the expression of messenger RNA for these cytokines in whole blood from M. paratuberculosis infected and uninfected cattle. Cytokine mRNA levels were examined before and after in vitro incubation with E.coli lipopolysaccharide (LPS) and lipoarabinomannan (LAM) purified from M. paratuberculosis. Uninfected calves, experimentally infected calves, and naturally infected cattle all displayed similar cytokine mRNA expression patterns. However, individual animals demonstrated variability in the levels of IL-6 and TNF-alpha mRNA expression as determined by a semiquantitative PCR method using 32P-labelled oligonucleotide probes.  相似文献   

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To obtain basic information on the state of proinflammatory cytokines in newborn calves, we determined the kinetics of 5 cytokines (IL-1beta, IL-6, TNF-alpha, IFN-gamma and IL-1 receptor antagonist) in sera of newborns during the first 4 weeks of life. At birth, none of the 5 cytokines were detected in almost all serum samples, but the cytokines became detectable within 12 hr after being fed colostram. The mean concentrations of the cytokines reached peak levels by 24 hr and then gradually decreased and became undetectable by 4 weeks after birth. Cytokine mRNA expressions in peripheral blood mononuclear cells of newborns were observed without reference to the cytokine concentrations in sera. Serum cytokines detected in newborn calves are probably colostral origin.  相似文献   

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The capacity of the two cytokines TNF-alpha and IL-1beta to directly stimulate the oxidative activity of polymorphonuclear neutrophils remains debated. The purpose of this study was to verify if a direct stimulation of equine neutrophils by TNF-alpha and IL-1beta was possible. Equine neutrophils were isolated from blood by discontinuous density gradient centrifugation. The cell viability after isolation was >98%. The neutrophils were used at 1.25 x 10(6) cells by assay, immediately after isolation. The oxidative activity of neutrophils was measured by luminol- or lucigenin-enhanced chemiluminescence (CL), and the CL was recorded for 60 min. TNF-alpha and IL-1beta were used at concentrations ranging from 0.001 to 100 ng (0.0017-167 ng ml(-1)) for 1.25 x 10(6) neutrophils, and added to the cells just before the CL measurement. Both cytokines highly stimulated the lucigenin-enhanced CL of equine neutrophils in a dose-dependent manner. TNF-alpha was already active at 0.001 ng and IL-1beta at 0.01 ng. The CL response obtained with TNF-alpha was maximal after 5 min and more pronounced with luminol than with lucigenin. With IL-1beta, the luminol-enhanced CL response of neutrophils was short-lived and inversely proportional to the cytokine concentration: the CL response returned to baseline after 12 min, and became even lower than the baseline value for 10 and 100 ng IL-1beta. As luminol (but not lucigenin) enters the cell, we hypothesized that a rapid intracellular consumption of the luminol molecules occurred, explaining the rapid and intense CL response. The choice of the CL enhancer used in previous CL studies of neutrophils stimulation by cytokines could perhaps explain that controversial results were reported. In conclusion, we demonstrated a direct activation of the oxidative activity of equine neutrophils by TNF-alpha and IL-1beta, which was dose-dependent and obtained with very low doses equivalent to the plasma concentrations measured for both cytokines in equine septic shock. TNF-alpha and IL-1beta can thus aggravate neutrophils oxidative activity during septic shock in horses.  相似文献   

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