Protective effect of dexamethasone in experimental bovine pneumonic mannheimiosis.
Clinical and experimental studies provide unequivocal evidence that neutrophils participate in the pathogenesis of lung injury in bovine pneumonic mannheimiosis (BPM). Since the inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 play a central role in the recruitment and activation of neutrophils, we hypothesize that pharmacological inhibition of their expression may prevent or reduce the inflammatory lung injury that is characteristic of the disease. The purpose of this study was to determine whether systemic therapy with dexamethasone sodium phosphate (DEX), a potent inhibitor of inflammatory cytokine synthesis, ameliorates disease development in an in vivo experimental model of BPM. Four experimental calves were treated intravenously with DEX (2 mg/kg 6 h prior to infection, 2 mg/kg immediately prior to infection, and 1 mg/kg every 12 h thereafter), while two placebo-treated control calves received dose-matched volumes of sterile saline. Disease was induced in the left lungs of the six calves by endobronchial administration of Mannheimia haemolytica. Clinical disease was characterized using a non-parametric scoring system, and the extent of gross pulmonary pathology affecting the left lung 48 h post-infection (PI) was determined using morphometric methods. Disease scores for DEX-treated calves were significantly lower than those for placebo-treated controls at all time points beyond 2 h PI (P<0.05) and the percent volume of the left lung exhibiting gross pneumonic lesions was significantly lower in DEX-treated calves (6.0+/-1.1%) as compared to controls (68.9+/-13.3%), P<0.05. In addition, histopathological lesions were less severe and extensive in DEX-treated calves. These findings indicate that pharmacological modulation of pulmonary inflammation may represent an alternative approach to control this disease. Successful implementation of this strategy will require additional research to identify drug agents that target the expression of cytokines and other inflammatory mediators without compromising host immune responses.
Department of Veterinary Pathobiology, University of Minnesota, St Paul, MN 55108, USA.
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C
Malazdrewich
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Thumbikat
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SK
Maheswaran
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002417:Cattle; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D008168:Lung / Q000473:pathology; D016978:Mannheimia haemolytica / Q000187:drug effects / Q000472:pathogenicity; D012766:Pasteurellosis, Pneumonic / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone