冬季猪群呼吸道疾病的防制要点

进入冬季以来,大部分猪场的猪只出现呼吸道疾病的情况比较严重,特别是北方地区,部分怀孕母猪和育肥猪群晚上干咳严重,呼吸相对紧促,个别猪只出现少许清澈鼻涕,白天     

Proinflammatory cytokines and viral respiratory disease in pigs

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.     

Survey of infectious agents involved in acute respiratory disease in finishing pigs.

Outbreaks of respiratory disease constitute a major health problem in herds of finishing pigs and their aetiology often remains unclear. In this study, 16 outbreaks of respiratory disease with acute clinical signs in finishing pigs were investigated to determine which infectious agents were involved. From each herd four diseased and two clinically healthy pigs were examined pathologically and for the presence of viruses, bacteria and mycoplasmas. In addition, paired blood samples from 10 groupmates of the diseased pigs were tested for antibodies against commonly known causal agents of respiratory disease. A clear diagnosis was possible in 12 of the 16 outbreaks. Seven were due to an infection with influenza virus and five were due to an infection with Actinobacillus pleuropneumoniae. A combination of influenza virus and A pleuropneumoniae may have caused one other outbreak, but no clear cause could be established for the other three outbreaks.     

Environment, respiratory disease, and performance of pigs in three Saskatchewan grower-finisher barns

A microcomputer-based environmental monitoring system was used to monitor temperature, humidity, and ventilation rate continuously in three commercial grower-finisher swine barns in Saskatchewan. During the monitoring period, a group of pigs in each barn was examined for growth rate, amount of lung affected with pneumonia, and degree of atrophic rhinitis. In addition, the total bacterial colony forming particle count within the airspace of each barn was measured once each week.

Significant differences existed among barns for daily maximum and minimum temperature, relative humidity, ventilation rate, and average bacterial colony forming particle counts. There was no difference among farms in the average percentage of lung affected with pneumonia, average snout atrophy score, or growth rate of the test animals.

On one farm, there was a significant positive correlation between snout score and percentage of lung affected with pneumonia. On another farm, there was a significant negative correlation between percentage of lung affected with pneumonia and growth rate.

     

Efficacy of tulathromycin in the treatment of respiratory disease in pigs caused by Actinobacillus pleuropneumoniae

The efficacy of a single dose of tulathromycin, a novel triamilide antimicrobial of the macrolide class, given at 2.5 mg/kg or 5 mg/kg bodyweight, or three daily doses of ceftiofur, given at 3 mg/kg bodyweight, was evaluated in pigs with respiratory disease induced experimentally with Actinobacillus pleuropneumoniae. On day 0, 100 pigs with clinical signs of respiratory disease were randomly assigned to groups of 25 pigs, which were treated with either saline, one of the doses of tulathromycin, or ceftiofur. The pigs' rectal temperatures and clinical scores for respiratory signs and general attitude were recorded daily until day 10. Animals withdrawn from the study for welfare reasons were recorded. On day 10, the animals remaining in the study were weighed, euthanased and examined postmortem. Three of the animals treated with saline and one of those treated with 2.5 mg/kg tulathromycin were withdrawn from the study, but none of those treated with 5 mg/kg tulathromycin or ceftiofur were withdrawn. The least squares mean bodyweight gains of the pigs treated with the antimicrobial agents were significantly (P<0.05) higher than that of the saline-treated group, and the least squares mean percentages of the total lung involvement and incidence of respiratory disease associated with A. pleuropneumoniae were significantly (P<0.05) lower, but there were no significant differences between the three groups of pigs treated with the antimicrobial agents.     

Proinflammatory cytokine expression in the lung of pigs with porcine circovirus type 2-associated respiratory disease

Porcine circovirus type 2 (PCV2) causes a significant health problem for the swine industry worldwide. In this study, we investigated the cytokine expression profiles (IFN-γ, IL-1α, IL-8, and IL-10) in the lungs of pigs with PCV2-associated respiratory disease. The mRNA expressions of IL-1α and IL-8 were significantly up-regulated in pigs with PCV2-associated respiratory disease, while IL-10 expression was not detected. These results suggest that the increased expressions of proinflammatory cytokines in the lungs may play an important role in the immunopathologic response in pigs with PCV2-associated respiratory disease.     

Immunopathogenesis of porcine reproductive and respiratory syndrome in the respiratory tract of pigs

Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) impairs local pulmonary immune responses by damaging the mucociliary transport system, impairing the function of porcine alveolar macrophages and inducing apoptosis of immune cells. An imbalance between pro- and anti-inflammatory cytokines, including tumour necrosis factor-α and interleukin-10, in PRRS may impair the immune response of the lung. Pulmonary macrophage subpopulations have a range of susceptibilities to different PRRSV strains and different capacities to express cytokines. Infection with PRRSV decreases the bactericidal activity of macrophages, which increases susceptibility to secondary bacterial infections. PRRSV infection is associated with an increase in concentrations of haptoglobin, which may interact with the virus receptor (CD163) and induce the synthesis of anti-inflammatory mediators. The balance between pro- and anti-inflammatory cytokines modulates the expression of CD163, which may affect the pathogenicity and replication of the virus in different tissues. With the emergence of highly pathogenic PRRSV, there is a need for more information on the immunopathogenesis of different strains of PRRS, particularly to develop more effective vaccines.     

The combination of PRRS virus and bacterial endotoxin as a model for multifactorial respiratory disease in pigs

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.     

Seroprevalence of porcine respiratory coronavirus in selected Korean pigs

A total of 446 serum samples from 88 herds in Korea were examined for antibody to porcine respiratory coronavirus (PRCV) using blocking enzyme-linked immunosorbent assay (ELISA). All serum samples were collected from 24- to 26-week-old finishing pigs between December 1998 and June 1999. By ELISA, 237 out of 446 sera tested (53.1%) and 54 out of 88 sampled herds (61.3%) were positive against PRCV. Of 446 sera from 88 herd tested, 185 (41.5%) serum samples from 22 (25%) herds were seronegative against PRCV and transmissible gastroenteritis virus infection. Our data suggested that seropositive herds for PRCV are distributed diffusely throughout South Korea.     

IgA immune responses in the respiratory tract of pigs

Experiments were conducted in a group of pigs to determine the ontogeny of antigen specific IgA in the trachea. The results showed that following intraperitoneal immunisation with ovalbumin (OVA) there were antigen specific IgG and IgA responses in both serum and respiratory tract secretion (RTS). After intratracheal challenge the IgA response in RTS was greater than that in serum as judged by the IgA/IgG ELISA ratios. Furthermore, following intratracheal challenge the IgA/IgG RTS ratio remained elevated for about 30 days. At slaughter, the anti-OVA containing-cell (AOCC) response and the corresponding immunoglobulin class were assessed using double fluorochrome labelling techniques. Pigs challenged intratracheally on four occasions between 11 and 67 days after intraperitoneal immunisation had a population of AOCC in the trachea which was 49 +/- 15 per cent IgA. In contrast, groups of pigs intraperitoneally immunised but challenged intratracheally on fewer occasions had significantly lower proportions of AOCC that were IgA. In conjunction with previous findings these results suggest that following intraperitoneal immunisation regular antigenic challenge of the trachea over an extended period leads to an increase in the proportion of AOCC which are IgA. These results are discussed in terms of the mechanisms involved in protecting the respiratory tract.     

BW755C modifies endotoxin-induced respiratory failure in pigs

The porcine pulmonary response to endotoxemia was evaluated before and after 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C), a dual inhibitor of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Escherichia coli endotoxin (055-B5) was infused IV into anesthetized 10- to 14-week-old pigs at 5 micrograms/kg the first hour, followed by 2 micrograms/kg/hr for 3.5 hours. The BW755C was infused at 20 mg/kg before endotoxin was administered and at 2.2 mg/kg during endotoxemia. During phase 1 (ie, 0 to 2 hours), the endotoxin-induced pulmonary hypertension, increased pulmonary vascular resistance and alveolar-arterial oxygen gradient, and decreased cardiac index and lung dynamic compliance were blocked or modified by BW755C. During phase 2 endotoxemia (ie, 2 to 4.5 hours), BW755C modified or blocked the increases in pulmonary vascular pressures, pulmonary vascular resistance, alveolar dead space ventilation, alveolar-arterial oxygen gradient, lung water, and bronchoalveolar lavage albumin concentration. The BW755C also modified the phase 2 decreases in cardiac index, lung dynamic compliance, and aortic platelet count. With regard to the endotoxin-induced pulmonary vasoconstriction, bronchoconstriction, and impairment of gas exchange, the data do not support a role for lipoxygenase metabolites, because the modified blockade (provided by BW755C) was of no greater magnitude than that reported for indomethacin (cyclooxygenase blocker). However, the data supports a possible role for lipoxygenase metabolites with regard to altering vascular permeability, cardiac index, and aortic platelet count.