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OJVRTM

Online Journal of Veterinary Research©

Volume 16 (3):96-103, 2012.

Pathology, dose response and tolerance to cyclophosphamide and as a model for immuno-suppression in sheep.

 

S Bhandari (BVSc, MSc)* §, CJ Charles (PhD)†, AP Miller, (Mb ChB)*, A Scott-Thomas, (PhD)*, ST Chambers, (Mb ChB, MD, MSc)*‡

 

*Department(s) of Pathology and †Medicine, University of Otago Christchurch, and ‡Department of Infectious Diseases, Christchurch Hospital, New Zealand

 

ABSTRACT

 

S Bhandari S, Charles CJ,  Miller AP, Scott-Thomas A, Chambers ST., Pathology, dose response and tolerance to cyclophosphamide and as a model for immuno-suppression in sheep, Online J Vet Res., 16 (3):96-103, 2012. Cyclophosphamide is one of the most common chemotherapy drugs used to produce immunosuppressed animal models of disease. This study was aimed at developing an immunosuppressed sheep model of invasive aspergillosis using cyclophosphamide. Six female Coopworth sheep were dosed with cyclophosphamide at 30, 45, 60 or 75mg/kg body weight with the intention of inducing neutropenia. There was a dose-dependent reduction in neutrophil count but this was mild and transient at doses of 30 and 45 mg/kg.  All animals dosed with 60 mg/kg had a nadir of less than 0.5 x109/L but this was relatively short-lived.  All animals showed respiratory distress and loss of appetite commencing as early as 24h following cyclophosphamide dosing with rapid deterioration of general health requiring euthanasia.  At post-mortem examination, the lungs of all the sheep showed features of diffuse alveolar damage (DAD) characterized by diffuse edema, focal alveolar hemorrhage, consolidation and congestion.  Bacterial and fungal culture of the lung homogenate was always negative. On the basis of these findings, it was concluded that these animals suffered from cyclophosphamide-induced DAD with acute respiratory distress syndrome and it was not possible to establish a sheep model of invasive aspergillosis.

 

 

Keywords: Cyclophosphamide-toxicity; Diffuse alveolar damage; Immunosuppression; Sheep.

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