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Anti-Inflammatories Can Help Minimizing lung tissue damage caused by white cells known as neutrophils may be one way to reduce losses due to bovine respiratory disease (BRD), says a Texas veterinarian. "It's the job of neutrophils to help fight infection by destroying bacteria," explains Dr. Breck Hunsaker, a veterinarian with Schering-Plough Animal Health Corporation. In the process, however, these white blood cells also release enzymes and toxic substances that damage tissues, such as blood vessels and capillaries. "If you looked under the microscope at lungs in cattle with BRD, the airways would be plugged with neutrophils," he says. The important role that neutrophils play in BRD is demonstrated by research that shows when the body is depleted of these white cells, the severity of damage to lung tissue isn't as great as when neutrophils are present, Dr. Hunsaker says. Controlled Studies In a controlled study conducted at Michigan State University, calves were inoculated with Pasteurella haemolytica -- the pathogen most often responsible for BRD. In some of the calves, the researchers did not alter the normal number of neutrophils. But in others, they administered hydroxyurea, a drug that reduces the number of neutrophils. When the groups of calves were compared, those with normal numbers of neutrophil levels had signs of lung injury such as low blood oxygen, a slowed heart rate, rapid breathing and lesions in the lung typical of BRD. These changes did not occur in the calves with depleted numbers of neutrophils. In addition, lungs in the neutrophil-depleted calves were no different from lungs in a third group of calves that also were neutrophil-depleted, but did not receive P. haemolytica, report R. F. Slocombe, BVSc, PhD and associates. The results indicate that neutrophils damage the lungs in calves with acute pulmonary pasteurellosis, and that neutrophil depletion appears to protect calves against lung injury, the investigators say. Extensive Alveolar Edema Found In another study conducted by investigators at the University of Tennessee, one group of calves received hydroxyurea to deplete neutrophils, and the other group served as controls and received saline. All calves were then inoculated with P. haemolytica. A rise in body temperature, indicating an acute inflammatory response, was found in both groups. Lung tissue damage occurred within six hours after inoculation in both groups, but the type of damage varied. For instance, in the group with normal numbers of neutrophils, there was edema, or fluid, in the lungs, fibrinopurulent alveolitis, bronchiolitis and necrosis or death of tissues with intravascular thrombosis. Alternatively, in the neutrophil-depleted group, there was edema in the lungs as well as hemorrhage at the inoculation sites, report Mike A. Breider and associates. "In other words," says Dr. Hunsaker, "there was tissue damage in both groups, but the infiltration of inflammatory cells and their effects were primarily limited to the neutrophil sufficient group. "It is well known that inflammation and lung damage in BRD is due at least in part by toxins that are released by bacteria resulting in a condition called endotoxemia. But this research shows that a lot of damage done in BRD is also caused by the body's own responses -- such as the infiltration of neutrophils," he says. Controlling Inflammation Separate research also indicates that it is possible to minimize lung damage with administration of an anti-inflammatory, he says. Dr. Hunsaker cites a Nebraska study showing that when cattle with BRD received Banamine (flunixin meglumine) in addition to an antibiotic, the lung sacs were not as filled with fluid due to inflamed tissue. In the study, 66 mixed-breed beef cattle with BRD received Banamine and an antibiotic, or an antibiotic alone. Those in the combination treatment group had far less inflammation and fewer lung lesions -- 1.7%, compared with 15.3% in the antibiotic-only group. Treated animals also had significantly lower rectal temperatures for the first 48 hours and more normal illness scores by day 3. Dr. Hunsaker points out that lung lesions at slaughter have been associated with reduced growth rates and are likely associated with increased relapse and reinfection rates. "Inflammation and fluid are often inevitable consequences of BRD, but we can combat them by treating with an anti-inflammatory. For producers, it could minimize the economic consequences of BRD, one of the most costly diseases affecting the cattle industry," he says. "It could be," Dr. Hunsaker speculates, that "Banamine minimizes the adverse effects of neutrophil infiltration and endotoxins, thereby reducing inflammation. If we reduce inflammation, we may reduce the amount of long term damage done to the lung during pneumonia." |
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