CYCLOPHOSPHAMIDE (CYTOXAN(R))-INDUCED HEMATOLOGIC ALTERATIONS IN SPECIFIC-PATHOGEN-FREE CHICKENS

Cyclophosphamide (Cytoxan(R)) was given at 75 mg/kg body weight via da ily intramuscular injections for 4 days to 3-week-old specific-pathoge n-free (SPF) chickens in an attempt to determine if heteropenia could be induced in chickens. Control birds were given a like quantity of ph osphate-buffered saline, the diluent for Cytoxan(R). Peripheral blood heterophil numbers were determined and monitored by total leukocyte an d 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 bi rd's baseline heterophil count (heteropenia). The effects of Cyroxan(R ) on trachea, lung, liver, kidney, bursa of Fabricius, bone marrow, sp leen, and thymus were determined by microscopic examination of those t issues collected the day following heteropenia. Cytoxan(R) had no effe ct on trachea, lung, liver, kidney, and thymus. Bursa of Fabricius and spleen had decreased amounts of lymphoid aggregates. Bone marrow of C ytoxan(R)-treated chickens was hypocellular. The study was then repeat ed to determine the reversibility of Cytoxan(R)-induced heteropenia. C ytoxan(R)-treated birds were allowed to recover until blood heterophil numbers equaled or exceeded those of control birds. Cytoxan(R), throu gh bone marrow suppression, induced a reversible heteropenia that deve loped between treatment days 10 and 12. In addition, Cytoxan(R) induce d a reversible lymphocytopenia between days 4 and 10 and a regenerativ e anemia between days 8 and 10. The ability to produce heteropenia in SPF chickens will allow the use of a heteropenic model for further stu dy of the heterophil's contribution to the inflammatory response.