Cyclophosphamide (Cytoxan(R))-induced hematologic alterations in specific-pathogen-free chickens

Cyclophosphamide (Cytoxan(R)) was given at 75 mg/kg body weight via daily intramuscular injections for 4 days to 3-week-old specific-pathogen-free (SPF) chickens in an attempt to determine if heteropenia could be induced in chickens. Control birds were given a like quantity of phosphate-buffered saline, the diluent for Cytoxan(R). Peripheral blood heterophil numbers were determined and monitored by total leukocyte and differential cell counts. Birds were grouped in pairs on day 0 based on total leukocyte count. The number of hererophils each bird had on day 0 served as a baseline heterophil count for that bird. Thereafter heterophil numbers were determined on the last day of drug treatment, and every other day until blood heterophil numbers were 20% of that bird's baseline heterophil count (heteropenia). The effects of Cyroxan(R) on trachea, lung, liver, kidney, bursa of Fabricius, bone marrow, spleen, and thymus were determined by microscopic examination of those tissues collected the day following heteropenia. Cytoxan(R) had no effect on trachea, lung, liver, kidney, and thymus. Bursa of Fabricius and spleen had decreased amounts of lymphoid aggregates. Bone marrow of Cytoxan(R)-treated chickens was hypocellular. The study was then repeated to determine the reversibility of Cytoxan(R)-induced heteropenia. Cytoxan(R)-treated birds were allowed to recover until blood heterophil numbers equaled or exceeded those of control birds. Cytoxan(R), through bone marrow suppression, induced a reversible heteropenia that developed between treatment days 10 and 12. In addition, Cytoxan(R) induced a reversible lymphocytopenia between days 4 and 10 and a regenerative anemia between days 8 and 10. The ability to produce heteropenia in SPF chickens will allow the use of a heteropenic model for further study of the heterophil's contribution to the inflammatory response.