Interactions of cold stress and Pasteurella haemolytica in the pathogenesis of pneumonic pasteurellosis in calves: changes in pulmonary function

Thirteen healthy neonatal Holstein calves were cold stressed twice by hosing with cold water for 20 minutes, 12 hours between hosings. Measurements of the pattern of ventilation [tidal volume (VT), respiratory frequency (f), minute ventilation (VMIN), and functional residual capacity (FRC)], gas exchange properties of the lungs [alveolar ventilation (VA), oxygen uptake (VO2), CO2 production (VCO2), dead space ventilation (VD), dead space/tidal volume ratio (VD/VT), arterial oxygen tension (PaO2), arterial CO2 tension (PaCO2) and alveolar-arterial oxygen difference (AaDO2)] and of the mechanical properties of the pulmonary system [dynamic compliance (Cdyn), pulmonary resistance (RL), and total respiratory system resistance (RRS)] were taken. Calves responded to chilling by increasing VO2 and VCO2 necessitating an increase in VA. This was accomplished by increasing VT with reciprocal decreases in f so that VMIN remained constant. There was no change in Cdyn, RL, or AaDO2. Seven of these 13 calves were then exposed to intratracheal inoculation of 2 X 10(9) organisms of Pasteurella haemolytica, the remaining calves serving as controls. Within 1 hour, calves exposed to P haemolytica had increased VMIN, f, VD/VT, and VD. There was a decrease in PaO2 associated with increased AaDO2, but no change in PaCO2, Cdyn or RL. By 3 hours after inoculation, there were pronounced changes in PaO2 and AaDO2, and Cdyn was reduced below base-line values. By 12 hours after inoculation, calves infected with P haemolytica had increased RL and RRS and PaCO2, in addition to the previously mentioned changes. Data from Pasteurella-exposed calves indicate that gas exchange impairment and peripheral lung injury occur rapidly and that increases in airway resistance develop relatively late in the disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental respiratory syncytial virus pneumonia in young calves: microbiologic and immunofluorescent findings

Young calves were inoculated with respiratory syncytial virus (RSV) intranasally or by a combined intranasal and intratracheal route and were killed between postinoculation (initial) days (PID) 1 and 14. Viral antigens were detected by immunofluorescence in nasopharyngeal cells from calves killed between PID 2 and 10. Evidence of infection of the trachea and lungs with RSV was obtained by immunofluorescence and virus isolation in calves inoculated by the combined route, but not in calves inoculated intranasally. Within the lungs, RSV antigens were observed in epithelial cells of bronchioli and alveoli. The only virus detected in inoculated calves was RSV. With the exception of 1 calf, bacteria or mycoplasmas were not isolated from the lower respiratory tracts of inoculated calves. Antibody to RSV was not detected in calves killed up to PID 5, but 4 of 5 colostrum-deprived calves killed between PID 10 and 13 had antibodies to RSV. Preexisting, maternally derived antibody to RSV did not protect the calves from infection. Seemingly, the clinical signs of pneumonia and pathologic lesions observed in inoculated calves were caused by RSV infection.     

Experimental bovine respiratory syncytial virus infection in conventional calves: ultrastructural respiratory lesions

The morphogenesis and repair of airway and alveolar injury induced by bovine respiratory syncytial virus (BRSV) was studied ultrastructurally in conventional calves to characterize pulmonary cell types susceptible to viral infection and cytopathologic changes associated with infection. Viral nucleocapsids and budding virions were present in tracheal and bronchial ciliated and nonciliated epithelial cells and mucous cells 3, 5, and 7 days after inoculation and in bronchiolar ciliated and nonciliated epithelial cells 5 days after inoculation. Mild interstitial pneumonia was observed 5 days after inoculation and was characterized by swelling of type 1 and type 2 alveolar epithelial cells, interstitial edema, and infiltration by lymphocytes and macrophages. Viral assembly and release in tracheal and bronchial epithelial cells was associated with loss of cilia from ciliated cells, formation of syncytial epithelial cells, swelling of mitochondria and endoplasmic reticulum, and cell necrosis. Neutrophils, lymphocytes, and macrophages were present in close association with the viral-infected and damaged epithelial cells. There was intercurrent hyperplasia of basal epithelial cells that, in association with other epithelial lesions, resulted in the loss of normal ciliated epithelium in these airways 5 and 7 days after inoculation. Regeneration of airway epithelium was largely completed by 10 days after inoculation, except in 1 of 4 calves that had failure of epithelial repair and that developed secondary bacterial pneumonia. Pulmonary ultrastructure in BRSV-inoculated calves 30 days after inoculation was indistinguishable from that in controls. The results demonstrated that BRSV can induce reversible alterations in airway epithelium, which may cause depression of mucociliary clearance and thereby enhance susceptibility to bacterial infection.     

Comparison of forced oscillation with the conventional method for histamine bronchoprovocation testing in horses

OBJECTIVE: To compare response of horses to histamine bronchoprovocation (HBP), using total respiratory resistance (Rrs) measured by forced oscillatory mechanics (FOM) with dynamic compliance (Cdyn) and pulmonary resistance (RL) measured by the esophageal balloon method. ANIMALS: 10 horses with various degrees of airway reactivity. PROCEDURE: The 2 methods for measuring airway responses to HBP were performed on separate days. Endpoints compared were increase of 150 or 200% of baseline Rrs (PC150Rrs, PC200Rrs) and to 150% of baseline RL (PC150RL) or decrease to 65% of baseline Cdyn (PC65Cdyn). Frequency dependence of respiratory mechanics, using FOM, was evaluated, using the slope of Rrs over 1 to 3 Hz and the ratios of Rrs at 1 Hz to Rrs at 2 and 3 Hz (Rrs1Hz/Rrs2Hz, Rrs1Hz/Rrs3Hz) and of Rrs at 2 Hz to Rrs at 3 Hz (Rrs2Hz/Rrs3Hz). Effect of histamine on frequency dependence was assessed. RESULTS: Correlation with PC65Cdyn was high for PC150Rrs (rs = 0.93) and PC200Rrs (rs = 0.96). Correlation between PC65Cdyn and PC150RL was weakly positive (rs = 0.61). The slope of Rrs over 1 to 3 Hz changed significantly between baseline (-0.07+/-0.09 cm H2O/L/s/Hz) and final histamine dose (-0.28+/-0.10 cm H2O/L/s/Hz). The Rrs1Hz/Rrs3Hz and Rrs2Hz/Rrs3Hz differed significantly (P < 0.05 between baseline [1.27+/-0.36 and 0.96+/-0.11, respectively] and final histamine dose [1.62+/-0.37 and 1.09+/-0.14, respectively]). CONCLUSIONS: Correlation between histamine-induced changes in respiratory mechanics, as measured by FOM and the pneumotachograph-esophageal balloon method, was good. The FOM results indicated frequency dependence of respiratory mechanics during HBP. CLINICAL RELEVANCE: A noninvasive method of measuring airway reactivity will facilitate routine evaluation of horses with suspected small airway disease and may be suitable for field studies.     

Studies on the pathogenesis and interspecies transmission of respiratory syncytial virus isolated from sheep

Inoculation of lambs with an ovine isolate of respiratory syncytial virus (RSV) by a combined intranasal and intratracheal route resulted in mild respiratory tract illness, with respiratory tract lesions. Lung lesions were characterized by bronchitis and bronchiolitis, hyperplasia of bronchial and bronchiolar epithelium, peribronchiolar and perivascular accumulations of lymphocytes, alveolar septal thickening, and collapse. Respiratory syncytial virus was recovered from the respiratory tract of inoculated lambs, and RSV antigen was demonstrated by immunoperoxidase staining of bronchiolar and alveolar epithelial cell in pneumonic lesions of lambs euthanatized on post-inoculation days 5 and 6. Other primary respiratory tract pathogens were not isolated. Clinical signs of respiratory tract illness or respiratory tract lesions did not develop in the in-contact control lamb. Inoculation of the ovine RSV isolate into calves and deer fawns resulted in infection in both species, and at necropsy, pneumonic lesions were present. A mild to moderate respiratory tract illness developed in the calves, but clinical disease was not seen in the fawns. Lung lesions in fawns were similar to those seen in lambs; lesions in calves were characterized by collapse, scattered areas of parenchymal necrosis, and bronchiolitis. Respiratory syncytial virus was reisolated from the lower respiratory tract of inoculated calves and fawns, and immunoperoxidase-positive epithelial cells were seen in pneumonic lesions. Other primary respiratory pathogens were not detected. Respiratory syncytial virus infection was not demonstrable in control animals that were in contact with inoculated animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory syncytial virus infection in transported calves

Nasal swab samples were collected from calves on individual farms in Tennessee and sequentially at an auction barn and at a feedlot to detect respiratory syncytial virus (RSV). In 1976, RSV was isolated from 5 of 225 calves at the auction barn and from 13 of 92 calves examined at the feedlot. Of the 13 isolations, 11 were from calves with acute respiratory tract disease. Most (14/18) calves infected with RSV were also shedding parainfluenza-3 virus in their nasal secretions. Attempts to isolate RSV in the 1977 study were unsuccessful, but there was serologic evidence of RSV infection. Most calves had serum antibody to RSV when examined initially at the farm or at the auction barn. Approximately 46% (46/99) of calves in the 1976 study and 71% (40/56) of calves in the 1977 study had a greater than or equal to 4-fold increase in serum antibody titer to RSV from auction barn to feedlot sample collection.     

Ultrastructural features of lesions in bronchiolar epithelium in induced respiratory syncytial virus pneumonia of calves

Ultrastructural changes were observed in bronchioles in acute and repair stages of respiratory syncytial virus pneumonia induced in eight young calves (calf Nos. 1-8) using a bovine strain of respiratory syncytial virus. Five of the calves were Friesians and three were Hereford x Friesians and all were male. Tissues from three mock-infected control calves (two Friesian, one Hereford x Friesian) were also examined. Calves were from 3 to 6 days old at the time of first inoculation, with the exception of calf No. 8, which was 2 weeks old. In the acute stage of the induced pneumonia, evidence of respiratory syncytial virus replication and release was demonstrable in both ciliated and non-ciliated bronchiolar epithelial cells, with the virus-releasing process most obvious at 4 and 5 days after infection. Respiratory syncytial virus infection of bronchiolar epithelium was associated with various changes, including hypertrophy, hyperplasia, and formation of syncytia. Necrosis of epithelial cell structures usually appeared to be preceded by their desquamation from bronchiolar walls. Respiratory syncytial virus infection resulted in considerable damage to the bronchiolar ciliary apparatus. Such damage was seen as early as 1 day post-infection and was still obvious at 10 days post-infection. Neutrophils were closely associated with respiratory syncytial virus infected epithelial cells and evidence of neutrophil fusion with infected epithelial cells was seen. These observations suggest that neutrophils may be involved in killing respiratory syncytial virus infected cells and that neutrophils might play an important role in early antiviral defense against respiratory syncytial virus at a time when antibody levels are low and other cellular defenses are not fully in play. Bronchiolar repair was evident from 6 days after infection and was well advanced at 10 and 13 days after infection.     

Efficacy of viral components of a nonabortigenic combination vaccine for prevention of respiratory and reproductive system diseases in cattle

Efficacy and safety of components of an IM-administered vaccine for prevention of infectious bovine rhinotracheitis virus (IBRV), parainfluenza type-3 (PI-3) virus, bovine viral diarrhea virus (BVDV), and respiratory syncytial virus (RSV) infections and campylobacteriosis and leptospirosis were evaluated in cattle, including calves and pregnant cows. Challenge of immunity tests were conducted in calves for IBRV, PI-3 virus, or BVDV vaccinal components. All inoculated calves developed serum-neutralizing antibodies and had substantially greater protection (as measured by clinical rating systems) than did controls after challenge exposure to virulent strains of IBRV, PI-3 virus, BVDV, or RSV. In in utero tests, IBRV or bovine RSV vaccinal strains were inoculated into fetuses of pregnant cows. Histologic changes or abortions did not occur after fetal inoculation of the RSV vaccinal strain, and 10 of 14 fetuses responded serologically. Of 9 fetuses, one responded serologically to the IBRV vaccinal strain after in utero inoculation and was aborted 3 weeks later. In an immunologic interference test, 10 calves vaccinated with 2 doses of the multivalent vaccine, containing the 4 viral components and a Campylobacter-Leptospira bacterin, developed serum-neutralizing antibodies to IBRV, PI-3 virus, BVDV, and RSV without evidence of serologic interference. Under field conditions, 10,771 cattle, including 4,543 pregnant cows, were vaccinated. Vaccine-related abortions did not occur.     

Effect of vaccination on cell populations in lung washes from calves after infection with respiratory syncytial virus

The inflammatory response in the air-passages of the lungs of calves after intranasal inoculation with respiratory syncytial virus (RSV) was compared in RSV-vaccinated and control animals. Total cells recovered from lung washings remained the same; however, the fold by eight days after infection and the type of cells changed from a predominance (85 per cent) of macrophages to equal proportions of macrophages and neutrophils (45 per cent) during the course of infection. The absolute numbers of neutrophils rose by 15-fold. In contrast, when RSV-vaccinated calves were challenged, the total number of cells recovered from lung washings remained the same; however, the numbers of macrophages decreased and the numbers of neutrophils increased by fivefold. Cytological studies of the lung washings revealed no evidence of an exacerbated inflammatory response in RSV-vaccinated calves. Levels of virus replication were significantly reduced in RSV-vaccinated compared with control animals.     

Effects of recombinant human alpha A interferon in gnotobiotic calves challenged with respiratory syncytial virus.

The effects of recombinant human alpha A interferon were studied in gnotobiotic calves challenged with respiratory syncytial virus (RSV). Gnotobiotic calves given doses of interferon by intramuscular injection over five days showed a marked, dose-related, rise in rectal temperature and depression of circulating leucocytes. Differential counts showed decreases in both lymphocytes and neutrophils. No significant pathological differences were found between treated and untreated calves, nor could any difference be demonstrated in the pattern of RSV infection.     

Comparison of the persistent efficacy of the injectable and pour-on formulations of doramectin against artificially-induced infection with Dictyocaulus viviparus in cattle

The persistent efficacy of the injectable and topical formulations of doramectin was compared against experimental challenges with infective larvae of Dictyocaulus viviparus in two separate studies. Four groups of 10 randomly-assigned calves, negative for lungworm larvae by the Baermann technique, were used in each study. Calves were treated subcutaneously in the midline of the neck or poured down the midline of the back with saline (1 ml/50 kg. injection: 1 ml/10 kg. pour-on) on Day 0 or doramectin (200 microg/kg = 1 ml/50 kg. injection: 500 microg/kg = 1 ml/10 kg. pour-on) on Day 0, 7, or 14. Two additional calves from the same pool of animals were randomly assigned as larval-viability monitors and received no treatment. Calves were inoculated daily with a gavage of approximately 100 larvae of D. viviparus from days 35 to 49 for the injectable study and days 28 to 42 for the pour-on study. The two larval viability monitor calves received approximately 3000 infective larvae in the same manner on Day 49 or 42 for the injectable and pour-on studies, respectively. Equal numbers of calves from each treatment group as well as the larval viability monitor calves were necropsied on days 14 and 15 after the last lungworm inoculation to enumerate the worm burden. The worms recovered were quantified and identified. For each study, geometric mean worm recoveries for each treatment group were back transformed from the natural log-transformed data (worm count +1) and were used to estimate percentage reduction. Doramectin injectable solution was 100.0% efficacious against lungworms for up to 49 days and the pour-on formulation was 100.0%, 93.1% and 81.5% effective in reducing lungworm infection resulting from challenge infection for up to 28, 35, and 42 days post-treatment, respectively.     

Pulmonary lesions induced by 3-methylindole and bovine respiratory syncytial virus in calves

Our objectives were to describe the ultrastructural morphogenesis of pulmonary lesions induced by 3-methylindole in 30- to 45-day-old Holstein calves and to determine whether toxic exposure to 3-methylindole exacerbates pulmonary lesions induced by bovine respiratory syncytial virus. Administration of 3-methylindole (0.25 g/kg) to calves resulted in interstitial edema and ultrastructural swelling of type-I alveolar epithelial cells and nonciliated bronchiolar epithelial cells as early as 4 to 6 hours after intraruminal administration. More severe alveolar edema containing protein was associated with swelling of capillary endothelial cells at 2 days after administration. Proliferation of type-II alveolar epithelial cells was first observed at 2 days after 3-methylindole administration, and marked hyperplasia of type-II epithelial cells and nonciliated bronchiolar epithelial cells was evident by 4 days after administration. Pulmonary cytochrome P-450 monooxygenase concentrations decreased significantly (P less than 0.001) by 12 hours after administration and did not increase significantly again by 8 days after administration. Calves were inoculated with bovine respiratory syncytial virus 3 days after administration of 3-methylindole, and pulmonary lesions were assessed 5 days after viral inoculation. Viral replication was demonstrated by fluorescence microscopy for viral antigen or by transmission electron microscopy in ciliated and nonciliated airway epithelial cells. Viral antigen was identified infrequently in alveolar macrophages and in type-II alveolar epithelial cells. 3-Methylindole exposure in calves did not result in more widespread distribution of viral antigen in alveolar tissue of respiratory syncytial virus-inoculated calves or in significant enhancement of viral pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental bovine respiratory syncytial virus infection in conventional calves: light microscopic lesions, microbiology, and studies on lavaged lung cells

Conventionally raised male Holstein calves, 1 month of age, were infected by intranasal and intratracheal inoculation with bovine respiratory syncytial virus. Viral antigen was identified by fluorescence microscopy most commonly in the cytoplasm of tracheal and bronchial epithelial cells 3 to 5 days after inoculation. Cytoplasmic viral antigen was identified also in nasal, nasopharyngeal, bronchiolar, and alveolar epithelial cells and in alveolar macrophages. Bronchitis and tracheitis, characterized in part by epithelial necrosis, formation of syncytial epithelial cells and epithelial hyperplasia, were the most common lesions observed histologically. Rhinitis, bronchiolitis, and interstitial pneumonia were observed less frequently. Alterations were not detected in the numbers of cells recovered by bronchoalveolar lavage after inoculation. An increase in the phagocytic rate of latex beads occurred in macrophages 5 days after inoculation. Viral-induced lesions were resolved by 30 days after inoculation. The results indicated that bovine respiratory syncytial virus inoculation of calves results in reversible alterations in airway epithelial structure and in the phagocytic function of alveolar macrophages.     

Comparative evaluation of ultrasonography and lung function testing with the clinical signs and pathology of calves inoculated experimentally with Pasteurella multocida

Seventeen calves were inoculated intratracheally with Pasteurella multocida 0 on three consecutive days with 10 ml of an inoculum containing 10(9) colony forming units/ml per day per calf. Before the first inoculation and 24 hours after the third, each calf was examined non-invasively by means of a clinical examination, chest ultrasonography, and impulse oscillometry to measure the impedance of the respiratory system. The inoculation of P multocida caused fever and a significant increase in respiratory rate and a decrease in tidal volume. There were also significant changes in the ultrasonographic results and in the impedance of the respiratory system. The percentage of the total surface area of the lungs showing pathological changes when the calves were euthanased 48 hours after the third inoculation ranged from 0.4 to 39 per cent. There were statistically significant correlations between the ultrasound scores and the pathological findings and between the ultrasound scores and the respiratory rate and tidal volume. The changes in the impedance of the respiratory system were not correlated with either the ultrasonographic or the pathological findings.     

Experimental reproduction of respiratory tract disease with bovine respiratory syncytial virus

An experiment was conducted to reproduce respiratory tract disease with bovine respiratory syncytial virus (BRSV) in one-month-old, colostrum-fed calves. The hypothesized role of viral hypersensitivity and persistent infection in the pathogenesis of BRSV pneumonia was also investigated. For BRSV inoculation a field isolate of BRSV, at the fifth passage level in cell culture, was administered by a combined respiratory tract route (intranasal and intratracheal) for four consecutive days. Four groups of calves were utilized as follows: Group I, 6 calves sham inoculated with uninfected tissue culture fluid and necropsied 21 days after the last inoculation; Group II, 6 calves inoculated with BRSV and necropsied at the time of maximal clinical response (4-6 days after the last inoculation); Group III, 6 calves inoculated with BRSV and necropsied at 21 days after the last inoculation; Group IV, 6 calves inoculated with BRSV, rechallenged with BRSV 10 days after initial exposure, and necropsied at 21 days after the initial inoculation. Clinical response was evaluated by daily monitoring of body temperature, heart rate, respiratory rate, arterial blood gas tensions, hematocrit, total protein, white blood cell count, and fibrinogen. Calves were necropsied and pulmonary surface lesions were quantitated by computer digitization. Viral pneumonia was reporduced in each principal group. Lesions were most extensive in Group II. Disease was not apparent in Group I (controls). Significant differences (p less than 0.05) in body temperature, heart rate, respiratory rate, arterial oxygen tension, and pneumonic surface area were demonstrated between control and infected calves. Results indicate that severe disease and lesions can be induced by BRSV in one-month-old calves that were colostrum-fed and seropositive to BRSV. BRSV rechallenge had minimal effect on disease progression. Based on clinical and pathological response, results did not support viral hypersensitivity or persistent infection as pathogenetic mechanisms of BRSV pneumonia.     

Effect of infection with bovine respiratory syncytial virus on pulmonary clearance of an inhaled antigen in calves

OBJECTIVE: To evaluate the effect of infection with bovine respiratory syncytial virus (BRSV) on clearance of inhaled antigens from the lungs of calves. ANIMALS: Eleven 6- to 8-week-old Holstein bull calves. PROCEDURES: Aerosolized (99m)technetium ((99m)Tc)-labeled diethylene triamine pentacetate (DTPA; 3 calves), commonly used to measure integrity of the pulmonary epithelium, and (99m)Tc-labeled ovalbumin (OA; 8 calves), commonly used as a prototype allergen, were used to evaluate pulmonary clearance before, during, and after experimentally induced infection with BRSV or sham inoculation with BRSV. Uptake in plasma (6 calves) and lung-efferent lymph (1 calf) was examined. RESULTS: Clearance of (99m)Tc-DTPA was significantly increased during BRSV infection; clearance of (99m)Tc-OA was decreased on day 7 after inoculation. Clearance time was correlated with severity of clinical disease, and amounts of (99m)Tc-OA in plasma and lymph were inversely correlated with clearance time. Minimum amounts of (99m)Tc-OA were detected at time points when pulmonary clearance of (99m)Tc-OA was most delayed. CONCLUSIONS AND CLINICAL RELEVANCE: BRSV caused infection of the respiratory tract with peak signs of clinical disease at 7 or 8 days after inoculation. Concurrently, there was a diminished ability to move inhaled protein antigen out of the lungs. Prolonged exposure to inhaled antigens during BRSV infection may enhance antigen presentation with consequent allergic sensitization and development of chronic inflammatory lung disease. IMPACT FOR HUMAN MEDICINE: Infection of humans with respiratory syncytial virus early after birth is associated with subsequent development of allergic asthma. Results for BRSV infection in these calves suggested a supportive mechanism for this scenario.     

Human and bovine respiratory syncytial virus: immunopathologic mechanisms

Human respiratory syncytial virus (HRSV) is the major respiratory tract pathogen of infants and young children. Bovine respiratory syncytial virus (BRSV) is recognised as an important cause of respiratory tract disease in calves. Both of these viruses and their respective diseases share many similarities. Immunopathologic mechanisms have been proposed to be involved in the pathogenesis of respiratory syncytial virus (RSV) infections. This review examines the current understanding of the role of immunopathologic mechanisms in RSV infections. The role of vaccines in inducing hypersensitivity is also examined. Additionally, non-immunopathogenic mechanisms involved in RSV infections are discussed.     

Increased pulmonary secretion of tumor necrosis factor-alpha in calves experimentally infected with bovine respiratory syncytial virus

Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease among calves in the Danish cattle industry. An experimental BRSV infection model was used to study the pathogenesis of the disease in calves. Broncho alveolar lung lavage (BAL) was performed on 28 Jersey calves, of which 23 were experimentally infected with BRSV and five were given a mock inoculum. The presence of the cytokine tumor necrosis factor alpha (TNF-alpha) in the BAL fluids was detected and quantified by a capture ELISA. TNF-alpha was detected in 21 of the infected animals. The amount of TNF-alpha in the BAL fluid of calves killed post inoculation day (PID) 2 and 4 was at the same very low level as in the uninfected control animals. Large amounts of TNF-alpha were detected on PID 6, maximum levels of TNF-alpha were reached on PID 7, and smaller amounts of TNF-alpha were seen on PID 8. The high levels of TNF-alpha appeared on the days where severe lung lesions and clinical signs were obvious and the amounts of BRSV-antigen were at their greatest. Although Pasteurellaceae were isolated from some of the BRSV-infected calves, calves treated with antibiotics before and through the whole period of the infection, as well as BRSV-infected calves free of bacteria reached the same level of TNF-alpha as animals from which bacteria were isolated from the lungs. It is concluded that significant quantities of TNF-alpha are produced in the lungs of the calves on PID 6-7 of BRSV infection. The involvement of TNF-alpha in the pathogenesis of, as well as the anti-viral immune response against, BRSV infection is discussed.     

Interaction of bovine respiratory syncytial virus with bovine alveolar macrophages in vivo: effects of virus infection upon selected cell functions.

The effect of bovine respiratory syncytial virus (BRSV) upon alveolar macrophage (AM) function was investigated using an in vivo calf inoculation model. Alveolar macrophages were collected sequentially from live calves at multiple time points during the 14 day period following viral inoculation. Alveolar macrophages from bronchoalveolar lavage fluids were purified by density gradient centrifugation (> 95% AM) prior to in vitro evaluation of cell functions. There were significant but variable and inconsistent differences in the functions of AM from the BRSV inoculated calves compared to the control calves. Fc-receptor mediated phagocytosis was either increased or unchanged by BRSV inoculation. Nonopsonized phagocytosis was decreased during the early postinoculation period and later increased. There was a variable effect on AM phagosome lysosome fusion with increased fusion activity on postinoculation days 2 through 5, 7 and 12 but reduced activity on days 6 and 10. The AM respiratory burst, as measured by nitroblue tetrazolium dye reduction, was essentially unaffected with a reduction in activity on day 10 only. In this model, BRSV inoculation of calves primarily resulted in an alteration of the membrane associated phagocytic functions of the alveolar macrophages (p < 0.05).     

The frequency, distribution and effects of antibodies, to seven putative respiratory pathogens, on respiratory disease and weight gain in feedlot calves in Ontario.

During 1983-85, 279 calves requiring treatment for bovine respiratory disease and 290 comparison (control) animals from 15 different groups of feedlot calves were bled on arrival and again at 28 days postarrival. Their sera were then analyzed for antibodies to seven putative respiratory pathogens. On arrival, the prevalences of indirect agglutination titers to Pasteurella haemolytica, P. haemolytica cytotoxin, Mycoplasma bovis and M. dispar were greater than 50%, the prevalence of titers to bovine virus diarrhea virus (BVDV) was approximately 40%, and the prevalences of titers to infectious bovine rhinotracheitis virus (IBRV), bovine respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) were all below 25%. Seroconversion during the first month after arrival occurred in more than half the calves to P. haemolytica cytotoxin, PIV3 and RSV. Seroconversion of agglutination titers to P. haemolytica, Mycoplasma and BVDV occurred in about 40% of calves, and seroconversion to IBRV was infrequent (less than 5%). Initial titers were negatively correlated to subsequent titer changes within organism. Initial titers, and titer changes between organisms were essentially independent. Light calves had an increased risk of being selected for treatment for respiratory disease. Seroconversion to P. haemolytica cytotoxin, RSV and BVDV were predictive of respiratory disease cases, explaining approximately 69% of all respiratory disease cases in the feedlots. It was not possible to accurately predict weight gain or relapse from the serological data.