TY - JOUR
T1 - Protective effect of dexamethasone in experimental bovine pneumonic mannheimiosis
AU - Malazdrewich, C.
AU - Thumbikat, P.
AU - Maheswaran, S. K.
N1 - Funding Information:
The authors are grateful to Dr David Hayden for assistance with interpretation of pulmonary histopathology, and to T. Dileepan for help with figure preparation. This study was supported by AVMA Foundation Research Grant 95-06 (to S.K.M.) and a grant from the Minnesota Agricultural Experiment Station (to S.K.M.).
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
KW - Bovine pneumonic mannheimiosis
KW - Dexamethasone
KW - Inflammatory cytokines
UR - http://www.scopus.com/inward/record.url?scp=1542297376&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1542297376&partnerID=8YFLogxK
U2 - 10.1016/j.micpath.2003.12.002
DO - 10.1016/j.micpath.2003.12.002
M3 - Article
C2 - 15001229
AN - SCOPUS:1542297376
SN - 0882-4010
VL - 36
SP - 227
EP - 236
JO - Microbial Pathogenesis
JF - Microbial Pathogenesis
IS - 4
ER -