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1.
Proinflammatory cytokines and viral respiratory disease in pigs   总被引:8,自引:0,他引:8  
Swine influenza virus (SIV), porcine respiratory coronavirus (PRCV) and porcine reproductive and respiratory syndrome virus (PRRSV) are enzootic viruses causing pulmonary infections in pigs. The first part of this review concentrates on known clinical and pathogenetic features of these infections. SIV is a primary respiratory pathogen; PRCV and PRRSV, on the contrary, tend to cause subclinical infections if uncomplicated but they appear to be important contributors to multifactorial respiratory diseases. The exact mechanisms whereby these viruses cause symptoms and pathology, however, remain unresolved. Classical studies of pathogenesis have revealed different lung cell tropisms and replication kinetics for each of these viruses and they suggest the involvement of different lung inflammatory responses or mediators. The proinflammatory cytokines interferon-alpha (IFN-alpha), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to play key roles in several respiratory disease conditions. The biological effects of these cytokines and their involvement in human viral respiratory disease are discussed in the second part of this review. The third part summarises studies that were recently undertaken in the authors' laboratory to investigate the relationship between respiratory disease in pigs and bioactive lung lavage levels of IFN-alpha, TNF-alpha and IL-1 during single and combined infections with the above viruses. In single SIV infections, typical signs of swine "flu" were tightly correlated with an excessive and coordinate production of the 3 cytokines examined. PRCV or PRRSV infections, in contrast, were subclinical and did not induce production of all 3 cytokines. Combined infections with these 2 subclinical respiratory viruses failed to potentiate disease or cytokine production. After combined inoculation with PRCV followed by bacterial lipopolysaccharide, both clinical respiratory disease and TNF-alpha/IL-1 production were markedly more severe than those associated with the respective single inoculations. Taken together, these data are the first to demonstrate that proinflammatory cytokines can be important mediators of viral respiratory diseases in pigs.  相似文献   

2.
The acute stages of infection with swine influenza virus (SIV), porcine respiratory coronavirus (PRCV) and porcine reproductive-respiratory syndrome virus (PRRSV) were shown to differ in terms of clinical and lung inflammatory effects and proinflammatory cytokine profiles in bronchoalveolar lavage (BAL) fluids. Caesarian-derived colostrum-deprived pigs were inoculated intratracheally with one of the three viruses. SIV infection was followed within 1 day post inoculation (d PI) by characteristic respiratory and general signs, and excessive lung epithelial desquamation and neutrophil infiltration (38 to 56 per cent of BAL cells at 1 d PI vs 0 to 1 per cent in controls). High concentrations of bioactive interferon-alpha (IFN -alpha), tumour necrosis factor-alpha (TNF -alpha) and interleukin-1 (IL -1) coincided with peak symptoms and neutrophil infiltration. PRCV infection was asymptomatic and produced a mild bronchointerstitial pneumonitis and neutrophil infiltration (13 to 22 per cent of BAL cells at 4 d PI). IFN -alpha titres parallelled those found during SIV infection, TNF -alpha was negligible and IL -1 undetectable. PRRSV infection induced anorexia and lethargy between 3 and 5 d PI. There was marked infiltration with mononuclear cells in alveolar septa and BAL fluids between 7 and 10 d PI, while neutrophils remained at less than 11 per cent of BAL cells at any time. IL -1 was produced from three throughout 10 d PI, while IFN -alpha production was minimal and TNF -alpha undetectable. These data strongly suggest that proinflammatory cytokines can be important mediators of viral respiratory disease.  相似文献   

3.
This paper reviews in vivo studies on the interaction between porcine reproductive and respiratory syndrome virus (PRRSV) and LPS performed in the authors' laboratory. The main aim was to develop a reproducible model to study the pathogenesis of PRRSV-induced multifactorial respiratory disease. The central hypothesis was that respiratory disease results from an overproduction of proinflammatory cytokines in the lungs. In a first series of studies, PRRSV was shown to be a poor inducer of TNF-alpha and IFN-alpha in the lungs, whereas IL-1 and the anti-inflammatory cytokine IL-10 were produced consistently during infection. We then set up a dual inoculation model in which pigs were inoculated intratracheally with PRRSV and 3-14 days later with LPS. PRRSV-infected pigs developed acute respiratory signs for 12-24h upon intratracheal LPS inoculation, in contrast to pigs inoculated with PRRSV or LPS only. Moreover, peak TNF-alpha, IL-1 and IL-6 titers were 10-100 times higher in PRRSV-LPS inoculated pigs than in the singly inoculated pigs and the cytokine overproduction was associated with disease. To further prove the role of proinflammatory cytokines, we studied the effect of pentoxifylline, a known inhibitor of TNF-alpha and IL-1, on PRRSV-LPS induced cytokine production and disease. The clinical effects of two non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam and flunixin meglumine, were also examined. Pentoxifylline, but not the NSAIDs, significantly reduced fever and respiratory signs from 2 to 6h after LPS. The levels of TNF-alpha and IL-1 in the lungs of pentoxifylline-treated pigs were moderately reduced, but were still 26 and 3.5-fold higher than in pigs inoculated with PRRSV or LPS only. This indicates that pathways other than inhibition of cytokine production contributed to the clinical improvement. Finally, we studied a mechanism by which PRRSV may sensitize the lungs for LPS. We hypothesized that PRRSV would increase the amount of LPS receptor complex in the lungs leading to LPS sensitisation. Both CD14 and LPS-binding protein, two components of this complex, increased significantly during infection and the amount of CD14 in particular was correlated with LPS sensitisation. The increase of CD14 was mainly due to infiltration of strongly CD14-positive monocytes in the lungs. The PRRSV-LPS combination proved to be a simple and reproducible experimental model for multifactorial respiratory disease in pigs. To what extent the interaction between PRRSV and LPS contributes to the development of complex respiratory disease is still a matter of debate.  相似文献   

4.
Cytokines in the pathogenesis of influenza   总被引:6,自引:0,他引:6  
Uncomplicated influenza in humans, horses or swine is characterized by massive virus replication in respiratory epithelial cells, inflammation and an abrupt onset of general and respiratory disease. There is now growing evidence that the so-called early cytokines produced at the site of infection mediate many of the clinical and pathological manifestations. Among these cytokines are interferon-alpha (IFN-alpha), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) alpha and beta, interleukin-6 (IL-6), interleukin-8 (IL-8) and monocyte-attracting chemokines. This paper reviews: (1) in vivo examinations of the cytokine profiles during influenza in mice, humans or swine; (2) in vivo data on the probable role of these cytokines; and (3) selected in vitro data on cytokine induction by the influenza virus. Examination of respiratory secretions of experimentally infected humans or animals revealed a brisk and concurrent rise in several of the cytokines mentioned. Moreover, peak cytokine levels directly correlated with virus replication and disease. In the mouse model, specific anti-cytokine strategies have further confirmed the role of cytokines in body temperature changes, anorexia and lung inflammation. However, cytokines were clearly not the only factor contributing to disease, and they seemed to be essential for resolution of the infection. Though influenza virus was shown to induce cytokines in cell culture, in vitro experiments have also revealed conflicting data. Furthermore, the viral genes or products that are responsible for cytokine induction are unknown. Exactly this information would make important contributions to our understanding of the genetic basis of viral virulence.  相似文献   

5.
Combinations of porcine respiratory coronavirus (PRCV) and either of two swine influenza viruses (H1N1 or H3N2) were administered intranasally and by aerosol to six- to eight-week-old specific pathogen-free pigs. The clinical responses, gross respiratory lesions and growth performances of these pigs were studied and compared with those of single (PRCV, H1N1 or H3N2) and mock-infected animals. PRCV infection caused fever, growth retardation and lung lesions, but no respiratory symptoms. Infection with swine influenza viruses caused rather similar, mild symptoms of disease, with H1N1 infection being the least severe. Combined infections with influenza viruses and PRCV did not appear to enhance the pathogenicity of these viruses. Furthermore, viruses were isolated more frequently from tissues and nasal swabs taken from 'single' than 'dual' infected animals, suggesting a possible in vivo interference between replication of PRCV and swine influenza virus.  相似文献   

6.
The role of swine torque teno sus viruses (TTSuVs) as co-factors in disease syndromes involving porcine circovirus strain 2 (PCV2) and porcine reproductive and respiratory disease syndrome virus (PRRSV) has been a debatable subject. In this study, the prevalence of TTSuVs in Iowa, the leading pork producing state in the U.S., was estimated by a duplex PCR. The PCR is capable of simultaneously detecting both teno sus viruses 1 and 2 (TTSuV1 and 2). Based on an analysis of 300 random samples representing six major geographical regions of the state, the overall prevalence rates for TTSuV1 and 2 were 47.34% and 24.67% respectively while the combined prevalence rate was 52.33%. The epidemiological association of TTSuV1 and 2 with the common etiological agents of the porcine respiratory disease complex (PRDC) namely porcine PRRSV, PCV2, Mycoplasma hyopneumoniae and swine influenza virus (SIV) was estimated in lung tissue derived from 45 pigs showing clinical signs of PRDC. Notably, 86.67% of the PRDC-suspect samples were positive for TTSuV1 in comparison to the baseline population prevalence rate of 47.34%. However, the prevalence of TTSuV2 (26.67%) was not significantly different. TTSuV1 was detected in 80.00%, 81.81%, 75.00% and 77.78% of the PRRSV, SIV, M. hyopneumoniae and PCV2 positive PRDC-suspect samples respectively. Our results indicate that TTSuV1 is strongly associated with clinical PRDC and support the hypothesis that TTSuVs might function as co-factors in PRDC. Further studies to define their possible role in the pathogenesis of swine respiratory diseases are warranted.  相似文献   

7.
8.
OBJECTIVE: To identify important pathogens and characterize their serologic and pathologic effects in porcine circovirus type 2 (PCV2)-infected pigs in relation to pig age and type of swine production system. DESIGN: Cross-sectional study. ANIMALS: 583 conventionally reared pigs. PROCEDURES: 3- (n = 157), 9- (149), 16- (152), and 24-week-old (125) pigs from 41 different 1-, 2-, and 3-site production systems (5 pigs/age group/farm) were euthanized and necropsied. Pigs with and without PCV2 infection were identified (via PCR assay); infection with and serologic responses to other pathogens and pathologic changes in various tissues (including lungs) were assessed. Logistic regression models were constructed for effects overall and within each age group and type of production system. RESULTS: Compared with PCV2-negative pigs, PCV2-positive pigs were more likely to have swine influenza virus (SIV) type A and Mycoplasma hyopneumoniae infections and sample-to-positive (S:P) ratios for SIV H1N1 from 0.50 to 0.99; also, PCV2-positive pigs had higher serum anti-porcine reproductive and respiratory syndrome virus (PRRSV) antibody titers and more severe lung tissue damage. Infection with SIV (but lower SIV H1N1 S:P ratio) was more likely in 3-week-old PCV2-positive pigs and evidence of systemic disease was greater in 16-week-old PCV2-positive pigs than in their PCV2-negative counterparts. By site type, associations of coinfections and disease effects between PCV2-positive and -negative pigs were greatest in 3-site production systems. CONCLUSIONS AND CLINICAL RELEVANCE: In PCV2-positive pigs, coinfections with SIV, M. hyopneumoniae, and PRRSV are important, having the greatest effect in the early to late nursery phase and in 3-site production systems.  相似文献   

9.
Porcine circovirus-2 and concurrent infections in the field   总被引:27,自引:0,他引:27  
Porcine circovirus-2 (PCV-2) is the necessary cause of post-weaning multisystemic wasting syndrome (PMWS) in swine; however, a variety of co-factors, including other infectious agents, are thought to be necessary in the full expression of disease. Porcine parvovirus (PPV) was found in the inoculum used in the first experiments to reproduce PMWS in gnotobiotic swine. Retrospective and prospective studies in the field and laboratory have demonstrated PCV-2 can act synergistically with PPV to enhance the severity of PMWS. PCV-2 has been shown to play a role in the porcine infectious disease complex (PRDC). Other co-infecting agents with PCV-2 in the lung include, porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV) and Mycoplasma hyopneumoniae. Exposure of pregnant sows to PPV, PRRSV, or encephalomyocarditis virus may interact with PCV-2 infected foetuses. The severity of hepatic lesions in PCV-2 infected pigs may be enhanced by co-infection with agents such as swine hepatitis E virus and Aujezsky's disease virus. Additional studies are required to determine the mechanistic basis for the interaction of PCV-2 with other agents in the pathogenesis of the various clinical syndromes that have been associated with PCV-2 infection.  相似文献   

10.
Qiao S  Feng L  Bao D  Guo J  Wan B  Xiao Z  Yang S  Zhang G 《Veterinary microbiology》2011,149(1-2):213-220
In 2006 China experienced outbreaks of a severe form of porcine reproductive and respiratory syndrome (PRRS) characterized by high fever, morbidity and mortality in swine irrespective of age. It is thought that secondary bacterial infections may contribute to the generation of this severe form of the disease. To determine the mechanisms by which a highly pathogenic PRRSV strain causes high fever we used an in vitro model to investigate the production of the pro-inflammatory cytokines IL-1β and TNF-α by macrophages in response to inoculation with PRRSV with or without LPS. Firstly we demonstrated, through an animal inoculation trial, that the isolate HN07-1 was a highly pathogenic strain and sequencing showed that the virus had the same genomic characteristics as previously described isolates. Porcine alveolar macrophage (PAM) cultures infected with PRRSV strains showed increased cytokine secretion and this was greater in the more virulent strain. Addition of LPS further increased cytokine secretion and again the effect was greater with the more virulent strain. Incubation of PAMs with PRRSV strain HN07-1 resulted in a significant increase in surface CD14 expression. This may explain the synergistic action between PRRSV and LPS in the induction of inflammatory cytokine secretion seen in the PAMs and so offer an explanation for the high fever that is characteristic of infections by the highly pathogenic PRRSV.  相似文献   

11.
Immunization of pigs with a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine initially elicits a weak interferon (IFN)-gamma response. To improve the immune response, an adjuvant consisting of plasmid encoding either porcine interleukin (IL)-12 or IFN-alpha was co-administered during vaccination. In the presence of either adjuvant, at least a three-fold increase in the primary virus-specific IFN-gamma response was observed. While this enhancement was only transient (1 week) when the IL-12 expressing plasmid was used, the effect was not only still apparent at 6 weeks after vaccination in the presence of the IFN-alpha expressing plasmid but even after challenge with a virulent genetically divergent PRRSV. In contrast, no effect of either adjuvant on the production of anti-virus antibodies was noticed throughout the study. Despite the apparent augmentation of a T helper (Th) 1 type response by the inclusion of IFN-alpha or IL-12 during vaccination, this modulation did not necessarily correlate with a reduction in viremia. Since a similar increase in the degree of the IFN-gamma response to the PRRSV vaccine could be achieved by substituting polyinosinic-polycytidylic acid in lieu of either cytokine, exposure to PRRSV in the presence of a variety of Th 1 polarizing molecules can positively influence the development of the cell-mediated immune response of swine to this pathogen. Conceivably, such intervention could be applied to improve the formulation of anti-PRRSV vaccines.  相似文献   

12.
Two common viral pathogens of swine, namely, porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV), were investigated in regard to their effects on monolayer cultures of swine alveolar macrophages (AMs). The purpose was to identify selected cellular changes and responses potentially associated with the clinical reactions of pigs infected with either or both of these viruses. Measurements included the (1) absolute and relative numbers of infected, viable, and apoptotic cells; (2) distribution of viral antigens; (3) levels of interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) produced and their association with the extent of virus-induced cytopathology. Four groups of AMs were studied, including mock-infected, PCV2 alone-infected (PCV2-A), PRRSV alone-infected (PRRSV-A), and PCV2 and PRRSV dually infected (PCV2/PRRSV) groups. The AMs of PCV2-A group had high antigen-containing rate without cell death. There was a marked increase in cell death and apoptosis in PRRSV-A group. However, a lower PRRSV-induced infectious rate, cell death, and apoptosis were seen in PCV2/PRRSV group. High levels of IFN-alpha production were detected in PCV2-infected groups, but not in mock-infected and PRRSV-A groups. The PRRSV-induced cytopathic effect (CPE) on MARC-145 cells or swine AMs was markedly reduced by pre-incubation of the cells with UV-treated or non-UV-treated supernatants of PCV2-infected AMs. In addition, the reduction in CPE was abolished when the supernatants of PCV2-infected AMs were pre-treated with a mouse anti-recombinant porcine IFN-alpha antibody. The results suggest that swine AMs were an important reservoir of PCV2; PCV2 infection reduced PRRSV infection and PRRSV-associated CPE in PCV2/PRRSV AMs; the reduction of PRRSV infection in AMs was mediated by IFN-alpha generated by PCV2 infection. The reduced PRRSV-associated CPE in AMs and increased pro-inflammatory cytokine production may lead to a more severe pneumonic lesion in those dually infected pigs.  相似文献   

13.
Lymphocyte subsets isolated from germ-free piglets experimentally infected with swine influenza virus (SIV), porcine reproductive and respiratory syndrome virus (PRRSV) or porcine circovirus type 2 (PCV2) were studied and the profile of these subsets among these three infections was monitored. Germ-free piglets were used since their response could be directly correlated to the viral infection. Because SIV infections are resolved even by colostrum-deprived neonates whereas PRRSV and PCV2 infections are not, SIV was used as a benchmark for an effectively resolved viral infection. PRRSV caused a large increase in the proportion of lymphocytes at the site of infection and rapid differentiation of B cells leading to a high level of Ig-producing cells but a severe reduction in CD2CD21+ primed B cells. Unlike SIV and PCV2, PRRSV also caused an increase in terminally differentiated subset of CD2+CD8α+ γδ cells and polyclonal expansion of major Vβ families suggesting that non-specific helper T cells drive swift B cell activation. Distinct from infections with SIV and PRRSV, PCV2 infection led to the: (a) prevalence of MHC-II+ T cytotoxic cells, (b) restriction of the T helper compartment in the respiratory tract, (c) generation of a high proportion of FoxP3+ T cells in the blood and (d) selective expansion of IgA and IgE suggesting this virus elicits a mucosal immune response. Our findings suggest that PRRSV and PCV2 may negatively modulate the host immune system by different mechanisms which may explain their persistence.

Electronic supplementary material

The online version of this article (doi:10.1186/s13567-014-0091-x) contains supplementary material, which is available to authorized users.  相似文献   

14.
A total of 198 pigs with tachypnoea and temperature >/= 40 degrees C were selected on a Spanish finishing unit, and their sera were examined for antibodies to Actinobacillus pleuropneumoniae (App), porcine reproductive and respiratory syndrome virus (PRRSV), Aujeszky' disease virus (ADV), and swine influenza virus (SIV). Eighty-nine point nine per cent of the pigs were seropositive to App, 88.6 per cent to PRRS, 73.0 per cent to ADV, and 30.6 per cent to SIV. Thirty-one pigs (15.6 per cent) were seropositive for App, PRRSV, ADV and SIV, and only one (0.5 per cent) was seronegative for all. Statistical association was assessed for dual infections but it was not found in any case (P > 0.05). Other parameters (dyspnoea, nasal discharge and coughing) were also recorded, and no significant associations between them and the presence of antibodies against any of the four infections was found.  相似文献   

15.
为了测定H1N1亚型猪流感病毒(swine influenza virus,SIV)对小鼠的致病性,本试验对A/swine/Guangdong/2/2012(H1N1)株SIV HA基因进行克隆及遗传分析,并将SIV尿囊液经鼻腔感染6周龄BALB/c小鼠,观察感染后小鼠的一般状况、器官系数和组织病理学变化,在病毒感染后第1、3和7天使用荧光定量PCR测定小鼠肺脏、脾脏、脑组织中7种细胞因子mRNA的表达量,研究其对小鼠的致病特性。结果显示,该病毒属于经典SIV,病毒经鼻腔感染后可引起小鼠活动减少、采食量降低,但无咳嗽和死亡;病理组织学变化为肺间隔较正常组织明显增厚,毛细血管明显扩张充血,周围肺泡腔呈代偿性肺气肿;小鼠肺脏、脾脏组织样本中IFN-α、IFN-β、IP-10、IL-1β、TNF-α、IRF-3和IL-10 mRNA含量在感染后第3天均显著升高(P<0.05),而脑组织样本中IL-1β和IL-10在小鼠攻毒后第3和7天均显著上调(P<0.05)。  相似文献   

16.
This study set out to investigate the cytokines and acute phase proteins (APPs) associated with the acute stages of experimentally-induced swine influenza virus (SIV) infection in 3-week-old, colostrum-deprived, caesarean-derived piglets. The piglets were inoculated intratracheally with 107.5 50% egg infective dose [EID50] Swine/Belgium/1/98 (H1N1) SIV and were euthanased at time-points between 0 and 120 h post-inoculation (PI). Broncho-alveolar lavage fluid (BALF), lung homogenates and sera were examined for inflammatory mediators by bioassay or ELISA. Interferon (IFN)-α, interleukin (IL)-6, IL-1 and tumour necrosis factor (TNF)-α peaked in BALF 24–30 h PI, when virus titres and the severity of clinical signs were maximal.Whereas IFN-γ and IL-12, but not IL-18, increased in tandem in BALF, serum cytokine concentrations were either undetectable or were up to 100-fold lower. The APP C-reactive protein (CRP) and haptoglobin peaked 24 h later than the cytokines and reached higher levels in serum than in BALF. In contrast, lipopolysaccharide (LPS)-binding protein (LBP) only increased in BALF. Lung virus titres tightly correlated with BALF IFN-α, IL-6, IL-1, TNF-α, IFN-γ and IL-12, as well as with serum IL-6, IFN-α and IFN-γ. Signs of disease correlated with the same cytokines in BALF and serum, as well as with BALF LBP and serum CRP. The findings suggest that IFN-γ and IL-12 play a role in the pathogenesis of SIV and that APPs are induced by cytokines. This influenza infection model may have value in assessing the therapeutic potential of cytokine antagonists.  相似文献   

17.
SIV与PRRSV、CSFV、PCV-2和PRV交叉感染的检测   总被引:2,自引:0,他引:2  
采用RT-PCR方法对37份疑似猪流感病毒(SIV)感染病料进行了病原学检测。同时,还运用PCR和RT-PCR方法对SIV阳性病料进行了猪繁殖与呼吸综合征病毒(PRRSV)、猪瘟病毒(CSFV)、猪圆环病毒2型(PCV-2)和猪伪狂犬病毒(PRV)目的基因片段的扩增。结果,扩增出了SIV特异目的基因片段,且4份病料都为混合感染,感染状况分别为SIV/PRRSV/PRV,SIV/CSFV/PRRSV三重感染,SIV/PCV-2和SIV/PRRSV二重感染。  相似文献   

18.
为建立特异、敏感的猪流感病毒(SIV)和猪繁殖与呼吸综合征病毒(PRRSV)的双重RT-PCR检测方法,本研究根据GenBank登录的SIV M基因保守序列和PRRSV美洲型毒株的N基因保守序列,设计合成了2对特异引物,通过对扩增条件的优化,建立检测SIV和PRRSV的双重RT-PCR方法.检测结果显示:该方法可同时扩增出SIV(345 bp)和PRRSv(520 bp)的特异性片段;而猪瘟病毒、猪伪狂犬病病毒、猪细小病毒、猪圆环病毒2型及阴性鸡胚尿囊液核酸扩增结果均为阴性;对SIV和PRRSV 2种病毒混合液的最小检出量分别为102 EID50/0.1 mL和103TCID50/0.1 mL.应用双重RT-PCR和病毒分离法对12份临床疑似样品进行对比检测,结果表明:除双重RT-PCR检测到双阳性的3份混合感染病料中1份未分离到PRRSV外,其余2份均分离出病毒.证明该方法具有良好的特异性、敏感性,可以用于临床样品的早期快速检测.  相似文献   

19.
A cross-sectional serological study was conducted in Bhutan between October 2011 and February 2012 to determine the prevalence of antibodies to classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2), swine influenza virus (SIV) subtype H1N1 and Aujeszky's disease virus (ADV). Furthermore, risk factors for the seropositive status were investigated.  相似文献   

20.
Porcine respiratory and reproductive syndrome virus (PRRSV) disease, one of the most economically significant viral diseases in the swine industry, is characterized by miscarriages, premature farrowing, stillborn pigs, and respiratory disease associated with death and chronic poor performance of nursing and weaned pigs. Interleukin-12 (IL-12) is a key component in driving the development of cell-mediated immunity as well as stimulating interferon-gamma (IFN-gamma) production from T cells and natural killer cells. Although some studies have investigated the use of IL-12 as a vaccine adjuvant in swine, little is known about its effectiveness as a treatment against viral diseases in swine. The present study investigated whether recombinant porcine IL-12 (rpIL-12) enhances the immune response and thereby diminishes the effects of PRRSV infection in young pigs. Interestingly, in vitro experiments demonstrated that rpIL-12 is capable of inducing swine pulmonary alveolar macrophages (PAMs), the target cells of PRRSV, to produce IFN-gamma in a dose and time dependent manner. In addition, in vitro studies also revealed that rpIL-12 treatment was capable of significantly reducing PRRSV viral titers in PAMs. In vivo administration of rpIL-12 significantly decreased PRRSV titers in the lungs and blood of infected animals. Furthermore, treatment with rpIL-12 prevented significant growth retardation in PRRSV-infected animals. Finally, in response to viral antigen recall challenge, PAMs isolated from rpIL-12-treated/PRRSV-infected animals produced greater amounts of IFN-gamma and lesser amounts of interleukin-10 than PAMs isolated from non-rpIL-12-treated/PRRSV-infected animals. Taken together our data indicate that treatment with rpIL-12 may provide an effective approach to control or ameliorate PRRSV-induced disease in swine.  相似文献   

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