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Anti-inflammatory benefits of tilmicosin in calves with Pasteurella haemolytica-infected lungs.

OBJECTIVES: To determine whether tilmicosin alters neutrophil infiltration or function, induces neutrophil apoptosis, and affects accumulation of leukotriene B4 (LTB4) or tumor necrosis factor-alpha (TNF-alpha) in lungs of calves experimentally infected with Pasteurella haemolytica. ANIMALS: 12 weight-ranked Holstein calves. PROCEDURE: Calves were given 25% propylene glycol vehicle (n = 5) or tilmicosin (10 mg/kg of body weight; n = 6) subcutaneously, 18 hours and 15 minutes before intratracheal infection with 2 x 10(8) P haemolytica organisms. Two unmanipulated calves served as controls in some experiments. Rectal temperatures were recorded 15 minutes before, and at 3-hour intervals after infection for 24 hours. Samples obtained from bronchoalveolar lavage performed 3 and 24 hours after infection were used to assess colonization by P haemolytica, and neutrophil infiltration. Neutrophil phagocytosis of P haemolytica, membrane leakage as determined by trypan blue exclusion, oxidative function as determined by nitro blue tetrazolium reduction, and apoptosis, using electron microscopy and DNA fragmentation ELISA, were determined. SOluble TNF-alpha and LTB4 were measured from supernatants from bronchoalveolar lavage samples, using ELISA. RESULTS: Treatment with tilmicosin resulted in significant (P < 0.05) clearance of P haemolytica and neutrophil apoptosis at 3 hours, and decreased concentration of LTB4 at 24 hours. Rectal temperatures, neutrophil infiltration, phagocytosis, oxidative functions, membrane leakage, and soluble TNF-alpha concentrations were not significantly affected by tilmicosin. CONCLUSION: Tilmicosin effectively controlled P haemolytica infection, induced neutrophil apoptosis, reduced pulmonary inflammation, and did not affect neutrophil infiltration or function. CLINICAL RELEVANCE: By inducing neutrophil apoptosis, tilmicosin prevents further amplification of inflammatory injury in P haemolytica-infected lungs.

Animals↗

Pasteurella multocida infection in Japanese quail (Coturnix coturnix japonica).

Three flocks of Japanese quail, approximately 75,000 birds each, experienced acute high mortality beginning at 24 to 28 days of age. Gross lesions were absent or were composed of either multifocal small pale areas on livers and spleens or lungs slightly darker in color than normal. Histopathology revealed multifocal splenic and hepatic necrosis and interstitial pneumonia. Pasteurella multocida, serotype 3,4, was isolated from affected tissues. The quail were successfully treated with chlortetracycline, and the organism was apparently eliminated from the premises by thorough cleaning, disinfection, and insect and rodent control. Experimental studies showed Japanese quail to be highly susceptible to disease caused by the P. multocida isolated from the affected flocks.

Animals↗

Pasteurella haemolytica infection in a Goeldie's monkey.

An adult male Callimico goeldii died spontaneously. At necropsy, small whitish foci were found randomly distributed on the liver surface. Histologically, the foci were composed of mixed inflammatory cells with predominant polymorphonuclear cell infiltration and central areas of necrosis. Microbiological cultures revealed a Gram-negative coccoid-bacilli with bipolar staining. Biochemical analysis revealed that the microorganism was Pasteurella haemolytica.

Animals↗

Serum levels of tumor necrosis factor-alpha in calves experimentally infected with Pasteurella haemolytica A1.

The purpose of this study was to document the levels of tumor necrosis factor-alpha (TNF) in serum of calves experimentally infected intratracheally with Pasteurella haemolytica A1 and to determine if elevated TNF levels correlate with development of pneumonic pasteurellosis in the bovine. Serum samples were collected at sequential time periods from 0 h to 72 h post inoculation with P. haemolytica. TNF levels in those sera were measured by a cytotoxicity assay utilizing the TNF-sensitive WEHI 164 mouse fibrosarcoma cell line. Serum TNF levels in infected cattle began to rise at 2 h post inoculation, peaked at approximately 8 h, and decreased to near control levels by 72 h. There was extreme variability in serum TNF among the inoculated animals with levels varying from 120 pg ml-1 to 5000 pg ml-1 at 8 h post inoculation. These levels did not correspond with the degree of lung involvement. All inoculated calves developed lesions of pneumonic pasteurellosis characterized by fibrinous pleuritis with necrotizing, hemorrhagic pneumonia. These results suggest that TNF is probably a significant inflammatory mediator involved in the pathogenesis of bovine pneumonic pasteurellosis.

Animals↗

Immediate responses in serum TNF alpha and acute phase protein concentrations to infection with Pasteurella haemolytica A1 in calves.

The concentrations of tumour necrosis factor-alpha (TNF alpha), serum amyloid A (SAA) and haptoglobin were determined in serum samples taken from four calves in the 10 hours after their intra-tracheal inoculation with Pasteurella haemolytica serotype A1. The concentration of haptoglobin did not increase but the concentration of SAA rose progressively from within two hours of inoculation. The concentration of TNF alpha reached a peak in all the animals two hours after inoculation but had returned to undetectable levels after a further four hours. TNF alpha is likely to be an important mediator of the acute phase response in cattle and SAA is a more rapid bovine acute phase protein than haptoglobin in its response to infection with P haemolytica.

Animals↗

Pasteurella anatipestifer infection in commercial meat-type turkeys in California.

A disease outbreak characterized by respiratory signs, occasional neurologic signs, and increased mortality in commercial meat turkeys from four separate companies in central California was investigated in the late summer and early fall of 1986. The disease syndrome affected turkeys from 6 to 15 weeks of age and caused a severe fibrinous pericarditis, perihepatitis, and airsacculitis. Bacteriologic and serologic examinations as well as virus- and chlamydia-isolation attempts initially failed to implicate an etiologic agent. Eventually culture attempts were made in a 5% CO2 incubator, resulting in isolation of Pasteurella anatipestifer. The disease syndrome was reproduced in young turkeys and broiler chicks inoculated with the organism.

Animals↗

Pasteurella multocida infection of poultry farm rats.

Thirty-four rat carcases from 11 poultry farms were examined for the presence of Pasteurella multocida; 14 out of 34 (41 per cent) proved positive after mouse inoculation, compared with five out of 34 (14 per cent) using media alone. No salmonellae were recovered from 27 rat carcases using enrichment media. Poultry pasteurellosis was present on two farms with infected rats and the same serotype was present in rats and poultry in those cases.

Animals↗

The observation of reactive thrombocytosis in New Zealand white rabbits in response to experimental Pasteurella multocida infection.

Reactive thrombocytosis is an increase in the circulating thrombocyte count secondary to a physiologic process within the body, often an infection. Reactive thrombocytosis is different than primary or essential thrombocytosis which is usually related to myeloproliferative neoplasia. Essential thrombocytosis is most common in adults, whereas reactive thrombocytosis is most frequently observed in children. Reactive thrombocytosis has been occasionally reported in cats, dogs and horses but has not been previously reported in the rabbit. Rabbits were challenged with virulent Pasteurella multocida. Hematologic, clinical, and culture assessments were performed prior to challenge, enabling each animal to serve as its own control. The questions asked were whether reactive thrombocytosis was a consistent phenomena and whether its presence and/or intensity was related to disease severity. All challenged rabbits demonstrated some degree of thrombocytosis in response to the infection, but individual rabbits were varied in their pattern of thrombocytosis. Elevations varied from intense to mild to undulating with durations of 1 to 11 days above 500 x 10(9)/L and 0 to 5 days above 650 x 10(9)/L. Correlation analysis was unable to demonstrate significant association between thrombocytosis, body temperature, leukocyte count, or the granulocyte lymphocyte ratio (all r < 0.2). No significant association between intensity of thrombocytosis and degree or type of pathologic lesions was observed. Thrombocytosis does not appear predictive of disease intensity or outcome. The data indicate that in the rabbit thrombocytosis is a consistent response to infection with P. multocida. Rabbits may serve as a model for the study of reactive thrombocytosis, in humans especially in children infected with Haemophilus sp., which are also a members of the bacterial family Pasteurellaceae.

Animals↗

A dot-immunobinding assay for the serodiagnosis of Pasteurella multocida infection in laboratory rabbits.

A dot-immunobinding assay was developed to detect serum IgG specific for lipopolysaccharide of rabbit isolates of P. multocida. The assay detected serum IgG as early as 1 week after experimental subclinical nasal infection, whereas 8 weeks were required to detect antibody by a gel diffusion precipitin test. The assay was more reliable than nasal cultures, in that up to 46% of 16 weekly nasal washings of some infected rabbits failed to yield P. multocida. The bacterial antigen (proteinase k digested cell lysate) used in the assay reacted with IgG that did not cross-react with lipopolysaccharide antigens of B. bronchiseptica, P. pneumotropica or P. hemolytica. The assay is sensitive and specific, easily performed, cost effective, requires no special laboratory instruments and provides a permanent easily stored record.

Animals↗

The immune response to experimental Pasteurella haemolytica infection in calves.

Four male dairy calves, ages 1-9 months, were inoculated intratracheally (IT), with log dilutions (1.5 X 10(3)-1.5 X 10(6)) of an isolate of P. haemolytica A-1. Doses of bacteria varied according to ages of the calves, older calves receiving the larger doses. All four calves became severely ill within 24 h after inoculation and antibiotic treatment was considered essential. Two months later the four calves remained healthy after IT injection of P. haemolytica, again given in log dilution (2.8 X 10(2)-2.8 X 10(5)). The control calf, given a dilution of only 28 viable P. haemolytica (plate count), developed severe respiratory infection 9 days post inoculation. Antibiotic treatment was given to this calf for 7 days, at which time recovery was evident. All five calves developed direct bacterial agglutination titers to P. haemolytica. Persistent leukocyte migration inhibition indexes of all calves were decreased by greater than or equal to 20% compared to their controls. Although the initial doses administered were low, the calves became ill. Most reports refer to massive doses necessary to produce primary disease and significant agglutination titers.

Agglutination Tests↗

The pharmacokinetics of chlortetracycline orally administered to turkeys: influence of citric acid and Pasteurella multocida infection.

A physiologically based pharmacokinetic model was developed to describe the absorption and disposition of chlortetracyline (CTC) in the healthy and diseased (fowl cholera) turkey. The CTC was given (with and without citric acid) as an oral (15 mg/kg) or i.v. (1 mg/kg) dose. When minerals (0.3 g/L Ca2+, 0.1 g/L Mg2+) were dissolved in the bird's drinking water, the model indicated that the addition of citric acid (mass ratio of 10 citrate: 1 CTC) increased the fraction of dose absorbed from 0.06 to 0.16; once absorbed, the fractions of drug eliminated by renal excretion, biliary secretion, and chemical decomposition were 50, 46, and 4%, respectively. The presence of fowl cholera appeared to increase plasma levels by increasing the intestinal permeability and lowering the hepatic and/or renal clearance.

Administration, Oral↗