Swine Respiratory Disease Research Articles

Identification of the Actinobacillus pleuropneumoniae serotype using PCR based- apx genes

Actinobacillus pleuropneumoniae ( A. pleuropneumoniae) is an important swine respiratory disease pathogen, which has at least 15 serotypes. There are several techniques for the serotyping of A. pleuropneumoniae, however, these techniques are time consuming. In this study, the polymerase chain reaction (PCR) technique was developed for serotyping A. pleuropneumoniae using a set of specific primer designated for the apxI, apxII, apxIII and apxIVA genes. By this PCR typing system, 10 out of the 13 reference strains of A. pleuropneumoniae were differentiated. However, it was not possible to distinguish serotype 2 from 8, serotype 5a from 5b and serotype 9 from 11. Each serotype of A. pleuropneumoniae showed its own products patterns. The PCR typing system was further applied for typing the field isolates of A. pleuropneumoniae and compared to that using the gel immunodiffusion (GID) technique. The results from both PCR and GID techniques were in accordance. Thus, the PCR typing system may provide a rapid and useful tool for typing the serotypes of A. pleuropneumoniae.

Cephalosporins in veterinary medicine - ceftiofur use in food animals.

Cephalosporins are an important class of antibacterial agents in use today for both humans and animals. Four generations of cephalosporins have evolved, all of which contain the beta-lactam sub-structure first found in penicillin. The range of cephalosporins available for use in food-producing animals, which is the subject of this review, is limited compared to humans. A few first- and second-generation cephalosporins are approved worldwide strictly for treatment of mastitis infections in dairy cattle. A third-generation cephalosporin, ceftiofur, and a fourth-generation cephalosporin, cefquinome, have been developed strictly for veterinary use. Cefquinome has been approved in several countries for the treatment of respiratory disease in cattle and swine, foot rot in cattle and for mastitis in dairy cattle. Ceftiofur has worldwide approvals for respiratory disease in swine, ruminants (cattle, sheep and goats) and horses and has also been approved for foot rot and metritis infections in cattle. Ceftiofur has also been approved in various countries for early mortality infections in day-old chicks and turkey poults. This review summarizes cephalosporin use in general terms, and provides an overview of ceftiofur, in terms of its spectrum of activity, indications, metabolism, and degradation in the environment. The safety of ceftiofur is also reviewed, with respect to food-animal residues, rapid metabolism and degradation, and non-persistence of ceftiofur in the environment. The environmental fragility of cephalosporins have not been explored generally, but may be an important characteristic of this antibiotic class with respect to safety of use in animals.

Effectiveness of a single intramuscular dose of ceftiofur hydrochloride for the treatment of naturally occurring bacterial swine respiratory disease

Objective: To evaluate the effectiveness of ceftiofur hydrochloride (HCl) administered once at 5.0 mg ceftiofur equivalents (CE) per kg bodyweight (BW) for treatment of naturally occurring bacterial swine respiratory disease (SRD). Methods: Pigs (3.6 to 24.5 kg) in eight commercial herds were enrolled in the study. Pigs that exhibited clinical signs of SRD were randomly assigned to receive one intramuscular (IM) injection of either ceftiofur HCl at 5.0 mg CE per kg BW (141 pigs) or placebo (137 pigs) on Day 0. Necropsies were performed and lung lesions scored by a veterinarian on pigs that died and on all surviving pigs on Day 14. Microbiological identification of bacterial organisms was performed on the lungs of all pigs. Results: Mortality rate was lower (P<.05) for the ceftiofur-treated pigs (2.1%) than for the placebo-treated pigs (7.3%). Rate of clinical cure (defined prior to the study), lung lesion scores, and percentage of pigs that gained at least 2.5 kg in the 14 days after enrollment did not differ for ceftiofur-treated and placebo-treated pigs. Body temperatures for ceftiofur-treated pigs were lower than for placebo-treated pigs on Days 1 and 3. Implications: A single IM injection of ceftiofur HCl at 5.0 mg CE per kg BW reduced mortality and body temperature (Days 1 and 3 after injection) for pigs with SRD associated with Actinobacillus pleuropneumoniae, Haemophilus parasuis, Pasteurella multocida, and Streptococcus suis. To effectively treat pigs for SRD, the standard, 3-day, full course therapy of ceftiofur HCl is recommended.

Role of the dermonecrotic toxin of Bordetella bronchiseptica in the pathogenesis of respiratory disease in swine.

Bordetella bronchiseptica is one of the etiologic agents causing atrophic rhinitis and pneumonia in swine. It produces several purported virulence factors, including the dermonecrotic toxin (DNT), which has been implicated in the turbinate atrophy seen in cases of atrophic rhinitis. The purpose of these experiments was to clarify the role of this toxin in respiratory disease by comparing the pathogenicity in swine of two isogenic dnt mutants to their virulent DNT(+) parent strains. Two separate experiments were performed, one with each of the mutant-parent pairs. One-week-old cesarean-derived, colostrum-deprived pigs were inoculated intranasally with the parent strain, the dnt mutant strain, or phosphate-buffered saline. Weekly nasal washes were performed to monitor colonization of the nasal cavity, and the pigs were euthanized 4 weeks after inoculation to determine colonization of tissues and to examine the respiratory tract for pathology. There was evidence that colonization of the upper respiratory tract, but not the lower respiratory tract, was slightly greater for the parent strains than for the dnt mutants. Moderate turbinate atrophy and bronchopneumonia were found in most pigs given the parent strains, while there was no turbinate atrophy or pneumonia in pigs challenged with the dnt mutant strains. Therefore, production of DNT by B. bronchiseptica is necessary to produce the lesions of turbinate atrophy and bronchopneumonia in pigs infected with this organism.

Effective methods for the production of immunoglobulin Y using immunogens of Bordetella bronchiseptica, Pasteurella multocida and Actinobacillus pleuropneumoniae

Swine respiratory diseases induce severe economic losses in the swine industry worldwide. Several methods have been developed and applied to control these diseases. However, there are still problems of disease control in the swine industry. Recently, egg yolk antibodies have been found to offer several advantages for disease control in animals and humans. In a previous study (24), antibodies to several causative pathogens of swine respiratory diseases were developed. However, several problems remained, especially in terms of reduced laying rates. Therefore, experimental vaccines were reformulated with various bacterial antigens of the swine respiratory diseases. After immunizing hens with the antigens, antibody profiles and other effects including laying rates were investigated and compared to those of the previous study. Profiles of antibody titers were very similar with those of the previous study. However, side effects, such as depression, weakness, reduction of laying rates and mortality, were dramatically lowered and laying rates were increased in hens injected with certain experimental vaccines. In particular, laying rates of hens injected with vaccines against atrophic rhinitis were increased up to 84% by injecting a vaccine composed of only the DNTs of B. bronchiseptica and P. multocida D:4. Efficacies of the vaccines against swine pneumonic pasteurellosis and pleuropneumonia were very similar with those of the previous study. These results suggest that new vaccines could be effective in the production of egg yolk antibodies against the causative agents of swine respiratory diseases.

Molecular Characterization of the Polymerase Gene and Genomic Termini of Nipah Virus

In 1998, Nipah virus (NV) emerged in peninsular Malaysia, causing fatal encephalitis in humans and a respiratory disease in swine. NV is most closely related to Hendra virus (HV), a paramyxovirus that was identified in Australia in 1994, and it has been proposed that HV and NV represent a new genus within the family Paramyxoviridae. This report describes the analysis of the sequences of the polymerase gene (L) and genomic termini of NV as well as a comparison of the full-length, genomic sequences of HV and NV. The L gene of NV is predicted to be 2244 amino acids in size and contains the six domains found within the L proteins of all nonsegmented, negative-stranded (NNS) RNA viruses. However, the GDNQ motif found in most NNS RNA viruses was replaced by GDNE in both NV and HV. The 3' and 5' termini of the NV genome are nearly identical to the genomic termini of HV and share sequence homology with the genomic termini of other members of the subfamily Paramyxovirinae. At 18,246 nucleotides, the genome of NV is 12 nucleotides longer than the genome of HV and they have the largest genomes within the family Paramyxoviridae. The comparison of the structures of the genomes of HV and NV is now complete and this information will help to establish the taxonomic position of these novel viruses within the family Paramyxoviridae.

Diagnostic approach to respiratory disease in swine: A practitioner's perspective

Diagnostic approach to respiratory disease in swine: A practitioner's perspective

Adenovirus-mediated expression of interleukin-1 receptor antagonist in swine cells in vitro and in vivo

Adenovirus-mediated gene delivery of anticytokines is a powerful tool for modulating the cytokine environment under conditions of respiratory disease. In order to determine the feasibility of cytokine modulation in the context of respiratory disease in swine, nonreplicating E1- and E3-deficient adenovirus constructs expressing a model protein, β-galactosidase, and an anticytokine, the IL-1 receptor antagonist (IL-1Ra), were evaluated for in vitro expression in porcine PK15 cells, and in vivo following endotracheal instillation into the lungs. β-Galactosidase and IL-1Ra were readily expressed in vitro in swine cells. Endotracheal administration of lacZ-containing adenovirus demonstrated that endothelial and epithelial cells in the alveolar spaces and bronchi of the middle and lower lobes were the principal sites of infection and expression, whereas β-galactosidase staining was not observed in the upper lobe. Endotracheal administration of IL-1Ra recombinant adenovirus resulted in sustained expression of IL-1Ra into the alveolar spaces, where it was recovered in a concentration of 660 pg/ml in 500 ml of lavage fluid, equivalent to 330 ng IL-1Ra, in the lungs 7 days after treatment. Moreover, in vivo instillation of nonreplicating adenovirus did not induce an inflammatory response in the 1-week time frame of the study period. Lung weight as a percent of body weight, serum zinc, serum amyloid A, leukocyte differentials, neutrophil activity, and TNF levels all were the same between untreated pigs and pigs treated with either recombinant adenovirus. The results indicate that the delivery of IL-1Ra to swine lungs via nonreplicating, recombinant adenovirus may be an effective method for in vivo modulation of IL-1 activity and investigation of cytokine involvement in respiratory disease pathogenesis.

Effect of temperature modulation and bvg mutation of Bordetella bronchiseptica on adhesion, intracellular survival and cytotoxicity for swine alveolar macrophages

Bordetella bronchiseptica causes respiratory disease in swine, yet there are no studies examining the interaction of B. bronchiseptica with swine alveolar macrophages. A swine isolate of B. bronchiseptica was able to adhere to, and survive intracellularly in, swine alveolar macrophages, but the relative ability of the bacteria to accomplish these functions was dependent on its phenotypic phase and culture conditions. More bacteria were observed extracellularly as well as intracellularly by immunofluorescent staining when B. bronchiseptica was cultured at 23°C as compared to 37°C. However, more bacteria cultured at 37°C were found surviving intracellularly after the macrophages were cultured with polymyxin B to kill extracellular bacteria. Similar results were seen in experiments performed with an isogenic Bvg − phase-locked mutant of B. bronchiseptica cultured at 37 or 23°C, indicating that another temperature dependent mechanism in addition to bvg may play a role in adhesion and intracellular survival . B. bronchiseptica was cytotoxic for swine alveolar macrophages in the Bvg + phase only. The cytotoxicity of B. bronchiseptica for alveolar macrophages, and its ability to survive phagocytosis, are no doubt important to escape from immune clearance mechanisms and establish infection, and could leave the host susceptible to secondary respiratory pathogens.

Intracellular accumulation, subcellular distribution, and efflux of tilmicosin in chicken phagocytes

Tilmicosin is a semi-synthetic macrolide antibiotic, currently approved for veterinary use in cattle and swine respiratory disease, and is in development for use in poultry mycoplasma air sacculitis. In order to provide an understanding of clinical efficacy, the in vitro interaction of tilmicosin with three types of chicken phagocytes (MQ-NCSU macrophages, monocyte-macrophages, and heterophils) was evaluated. After incubation with radiolabeled tilmicosin, uptake was determined and expressed as the ratio of the cellular (Cc) to the extracellular (Ce) drug concentration (Cc:Ce). Tilmicosin was avidly accumulated by heterophils (Cc: Ce 138 at 4 h incubation vs 32 and 66, respectively, in MQ-NCSU and monocyte-macrophages) with 61 to 88% localized in the lysosomes. Uptake was dependent on cell viability, temperature, and pH, but was not influenced by metabolic inhibitors. However, phagocytosis of Pasteurella multocida and lipopolysaccharide exposure increased tilmicosin uptake by the chicken phagocytes. Upon removal of extracellular tilmicosin, 50% of the intracellular tilmicosin was effluxed within the first 30 min, but after 4 h of incubation in antibiotic-free medium, 30% remained cell-associated. Opsonized P. multocida significantly enhanced the release of tilmicosin from all three types of chicken phagocytes. Tilmicosin uptake was observed to increase lysosomal enzyme (acid phosphatase, lysozyme, avidin, and beta-glucuronidase) production. Finally, neutrophils were shown to transport and efflux bioactive tilmicosin in a test system measuring both neutrophil chemotaxis under agarose and a bioassay measuring inhibition of bacterial growth in the presence of antibiotic in agar. These in vitro observations of cellular pharmacology suggest a complex interaction between phagocytes and tilmicosin that contribute to clinical efficacy.

Intracellular accumulation, subcellular distribution and efflux of tilmicosin in swine phagocytes.

Tilmicosin is a semi-synthetic macrolide antibiotic, currently approved for veterinary use in cattle and swine respiratory disease. As the concentrations of tilmicosin are generally low in swine lung tissue, the interaction of tilmicosin with three types of swine phagocytes (monocyte-macrophages, alveolar macrophages, and neutrophils) was evaluated to provide an understanding of clinical efficacy. After incubation with radiolabelled tilmicosin, uptake was determined and expressed as the ratio of the intracellular (Ci) to the extracellular (Ce) drug concentration (Ci/Ce). Tilmicosin was avidly accumulated by the swine phagocytes (Ci/Ce 48-69 at 4 h incubation) with 51 to 85% localized in the lysosomes. Uptake was dependent on cell viability, temperature and pH, but was not influenced by the metabolic inhibitors, sodium cyanide or potassium fluoride. However, lipopolysaccharide (LPS) exposure increased tilmicosin uptake by the swine phagocytes. In neutrophils, upon removal of extracellular tilmicosin, 60% of the intracellular tilmicosin was effluxed within the first 30 min, but after 4 h of incubation in drug-free medium, 25% remained cell-associated. In contrast, after 4 h of incubation in drug-free medium, 60% and 45% of tilmicosin remained cell-associated, within alveolar macrophages and monocyte-derived macrophages, respectively. Tilmicosin uptake was observed to increase lysosomal enzyme (acid phosphatase, lysozyme and beta-glucuronidase) production. Finally, neutrophils were shown to transport and efflux bioactive tilmicosin in a test system measuring both neutrophil chemotaxis under agarose and a bioassay measuring inhibition of bacterial growth in the presence of antibiotic in agar. These in vitro interactions of tilmicosin with swine phagocytes suggest an integral role in effecting clinical efficacy.

Relationships Between Selected Climatic Factors in Fattening Units and their Influence on the Development of Respiratory Diseases in Swine

The correlation between climatic parameters with one another in fattening units and the influence of environmental factors on lung lesions registered at slaughter were studied in 6 integrated herds with continuous production systems. In addition, the influence of environmental parameters on the spread of Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae (serotypes 2 and 3) and on the productivity was monitored in 2 specialized fattening herds with strict batch production. The outdoor temperature was positively correlated to the indoor temperature, but negatively correlated to the relative humidity and the concentration of carbon dioxide in the stables. These indoor parameters were also correlated to each other. The concentration of ammonia was not correlated to any other climatic parameter. No correlation between the climatic parameters measured and the prevalences of pneumonia and pleuritis registered at slaughter was shown. The rapidness in spread of mycoplasmosis seemed to be more dependent of the antibody status of the pigs on arrival than on the climate of the units. In contrast, a correlation between the climatic parameters and the spread of the less contagious infection (Actinobacillus) was indicated. The influence of the climatic parameters on the daily weight gain was not ensured.

Porcine reproductive and respiratory syndrome virus (PRRSv) interaction with Haemophilus parasuis

The interaction of bacteria and virus has been well demonstrated in the pathogenesis of respiratory disease in swine. The interaction between porcine respiratory and reproductive syndrome virus (PRRSv) and Haemophilus parasuis has not been studied. We initiated studies to evaluate a possible effect of the PRRSv on the pathogenesis of polyserositis caused by H. parasuis. A group of 30 three week old piglets were distributed in 4 groups. Group I (10 pigs) was inoculated with PRRSv and H. parasuis. Group II (10 pigs) was inoculated with H. parasuis alone. Group III (5 pigs) was inoculated with virus alone and group IV (5 pigs) was inoculated with culture media. Lesions consisted of a severe fibrinous polyserositis affecting 7 of 10 animals in group II and a mild fibrinous pleuritis in 1 of 10 animals of group I. Three of ten animals dually infected with the two agents died during the course of the study. These animals had pulmonary congestion and focal lung hemorrhages. No other animals died from other groups. Group III and IV had no macroscopic lesions. Microscopically group III had interstitial pneumonia. Immunomodulating virus effect may explain the differences in terms of lesions severity between groups I and II. Septic shock was suspected as cause of sudden death.

Colonization of the tracheal epithelium of pigs by filamentous bacteria resembling cilia-associated respiratory bacillus.

Warthin Starry staining revealed filamentous bacteria colonizing the tracheal epithelium of 41 of 88 (46.6%) pigs submitted for necropsy at 2 midwestern veterinary diagnostic laboratories. The bacteria were interspersed between and oriented parallel to the cilia. In 4 of 4 colonized pig tracheas, filamentous bacteria were demonstrated by transmission electron microscopy. The bacteria were approximately the same length and diameter as cilia, and in areas of heavy colonization the bacteria outnumbered cilia. The filamentous bacteria were similar in location and morphologic characteristics to cilia-associated respiratory (CAR) bacilli of rats, mice, rabbits, and cattle. Results of immunoperoxidase staining and polymerase chain reaction analysis indicated that the pig CAR bacillus is a different bacterium than the rat CAR bacillus. Rat CAR bacillus causes chronic respiratory disease in rats and mice. The association, if any, between pig CAR bacillus and swine respiratory disease is unknown.

Disposition of Ceftiofur Sodium in Swine following Intramuscular Treatment

Ceftiofur displays a broad spectrum of bactericidal activity against both Gram-positive and Gram-negative bacteria including β-lactamase-producing strains. Three to five milligrams of ceftiofur per kilogram of body weight injected intramuscularly (im) on three consecutive days at 24-h intervals is recommended for bacteria-associated respiratory disease in swine. Metabolism studies in 12 swine given 5 mg of [ 14 C]ceftiofur/kg of body weight im for 3 consecutive days showed that 61.8±4.7% of the dose was excreted in urine and 10.8±5.1% of the dose was excreted in feces. The highest blood residues of about 15 ppm of [ 14 C]ceftiofur free acid equivalent were observed at 2 h after treatments, which declined to ∼2 ppm at 24 h. Almost all of the radioactivity in the blood was found in the plasma, suggesting that the drug did not penetrate the erythrocytes. Most of the radioactivity was bound to macromolecules in the plasma and tissues. Desfuroylceftiofur glutathione disulfide was found only in the liver and 3,3'-desfuroylceftiofur disulfide (dimer) only in the urine. Desfuroylceftiofur cysteine disulfide was present in plasma, tissues, and urine. The structures of the metabolites were deduced from HPLC comparison with synthetic standards, proton NMR, and thermospray mass spectrometry. Polar metabolites are present in urine and tissues after 12 h of treatment, indicating β-lactam and cepham ring opening. Details of disposition of ceftiofur in swine are presented and compared with rats from multiple oral dosing

Types of farm management as risk factors for swine respiratory disease

This study used the results of factor analysis described in a previous paper (D. Hurnik, I.R. Dohoo, A. Donald and N.P. Robinson, 1994. Factor analysis of swine farm management practices on Prince Edward Island. Prev. Vet. Med., 20 (1994) 135–146) to describe the role of the farm environment in respiratory disease of swine. The factors (farm type descriptions) were analysed using regression with prevalence estimates of enzootic pneumonia on 69 swine farms. Farms were dichotomized on enzootic pneumonia prevalence greater or less than 10%. Multiple logistic regression analysis of the dichotomized data revealed that three farm types had an increased risk of having enzootic pneumonia. Multiple source feeder barns (farm Type 4) with low emphasis on disease entry and control had an odds ratio of 2.38, meaning that farms closely matching this farm type were over twice as likely to have enzootic pneumonia for every one unit increase in the factor score. Family farms using floor feeding methods (Factor 5) had an odds ratio of 3.31, suggesting that this combination of management styles may be a contributing factor in enzootic pneumonia. Integrated farms (Factor 6) had an odds ratio of 2.31 for having the condition, suggesting that larger farms that mill their own feed and are closer in proximity to other pig farms have a greater chance of having enzootic pneumonia. A linear regression of the prevalence estimates of enzootic pneumonia on positive farms revealed that only farms with multiple source feeder barns and floor fed family farms were associated with a higher prevalence of enzootic pneumonia. Farms with extensive pig housing (Factor 1) were associated with a lower prevalence, suggesting that farms with ample pen space and air volume had fewer pigs with enzootic pneumonia. A similar analysis for pleuritis found a lower odds of lesions on farms with extensively housed pigs. This study confirmed that many commonly accepted risk factors, in combination, did indeed increase the likelihood of enzootic pneumonia. One previously unrecognized risk factor involved family farms that tended to floor feed. Determining whether the individual variables highly correlated with this factor are truly risk factors for enzootic pneumonia requires more study. Factors affecting enzootic pneumonia appeared to be different than those affecting pleuritis. Environmental influences are often discussed generally. This study indicates that the environment-disease interactions are different for the two diseases.

Factor analysis of swine farm management practices on Prince Edward Island

This study used multivariable analysis to describe the role of the environment in respiratory disease of swine. Environmental effects acting on pigs were assessed by visiting 76 pig farms on Prince Edward Island, Canada. Management areas examined were farm size, growth rate, feeding styles and feedstuffs, manure handling and bedding, ventilation, pen space and flooring, moving and mixing pigs, sources of pigs, people contact in the barn, labour source and experience. Data were gathered by physically measuring dimensional parameters, and by visual determination of other characteristics. One person performed the farm visits in a consistent manner. From the examination of the 76 farms, 43 management variables were calculated. The 43 variables were condensed using factor analysis into six factors. The factors are six uncorrelated variables that describe the 43 correlated management variables in a more statistically efficient manner. The six factors describe farm types based on which management variables score highly with each factor. The farm types that emerged were as follows: (1) smaller farms using extensive farming techniques—high volume and space per pig and straw as bedding; (2) a farm type using group pig flow, a system that used solid pen partitions, did not move pigs between pens, and a higher ratio of pigs to water spaces; (3) a farm type with room pig flow that was larger (pigs sold) than others in this study population, was farrow-to-finish and had modern facilities; (4) farms that bought pigs from different sources, did not seek veterinary advice, and had slow-growing pigs; (5) a family farm type that primarily floor fed the pigs; (6) an integrated farm type that was larger than average, made its own feed, was closer in proximity to other farms and had other farmers as primary visitors. The six farm types were biologically plausible descriptions of farm management on Prince Edward Island. The results of the factor analysis were then used in a regression analysis of enzootic pneumonia and pleuritis prevalence at slaughter. The results and conclusions of these analyses are presented in a subsequent paper.

Environmental factors affecting the severity of pneumonia in pigs

The variable manifestations of respiratory problems in finishing pigs have led to the concept of a multiple-factor aetiology for swine respiratory disease and in particular for enzootic pneumonia. The primary and secondary agents of the disease produce their most detrimental economic effects and the highest levels of mortality and morbidity during the finishing period, when the economics of production necessitate indoor housing and intensification. This paper considers the contribution of four main groups of environmental factors to the high levels of clinical disease and lesions which are found whenever large numbers of pigs are examined at slaughter. They are meteorological factors, population and social factors, management factors and airborne pollution.

Detection of tumor necrosis factor α from porcine alveolar macrophages using an L929 fibroblast bioassay

Tumor necrosis factor plays a central role in the mediation of the pathophysiological sequelae of infection and inflammation in animals and humans. The elucidation of its role in respiratory disease of swine has not been investigated, due in part to the lack of a sensitive and specific quantitative assay for its presence in tissue and fluid samples. Here we describe the detection of porcine tumor necrosis factor utilizing L929 murine fibroblast cells and characterize various parameters affecting assay sensitivity. Plating cell density and length of exposure time to test supernatants were the most critical factors. Using standard assay conditions as described here, porcine tumor necrosis factor was detected in alveolar macrophage conditioned media diluted more than 400-fold. Specificity of the assay for porcine tumor necrosis factor was shown by inhibition of cytotoxicity with neutralizing polyclonal antibodies for human recombinant tumor necrosis factor. Furthermore, comparisons of bioactivity with tumor necrosis factor mRNA levels from lipopolysaccharide-stimulated porcine alveolar macrophages indicated that the L929 bioassay was specific for porcine tumor necrosis factor.

Activated porcine alveolar macrophages: Are biological response modifiers the answer?

We report that 75% of conventionally housed 3- to 4-week-old swine already have detectable activated alveolar macrophages as measured by cytotoxicity of tumor cells. These macrophages can not be further activated by the biological response modifier N-acetylmuramyl-L-alanyl-D-isoglutamine-2H 2O (MDP). These macrophages lose cytotoxic activity when cultured for 24 h and this loss of activity can not be reversed by MDP. We suggest that MDP biological response modifier therapy of swine alveolar macrophages may not be a useful technique in preventing respiratory disease in swine.