Tilapia (Oreochromis niloticus) dosed with azathioprine display immune effects similar to those seen in mammals, including apoptosis

Azathioprine, an anti-neoplastic drug and therapeutic immunosuppressant, wa s administered intraperitoneally at 10.0 and 50.0 mg/kg to 3-6-month-old ti lapia (Oreochromis niloticus). Consistent alterations in immune cellular pa rameters of the blood, pronephros (hematopoietic kidney) and spleen were ob served. Peripheral blood total cellularity decreased as the azathioprine do se increased, to approximately half that of the control. Differential analy sis of white blood cells indicated a decline in lymphocyte number, in parti cular, with increased dosage of azathioprine. Pronephric total cellularity was depressed in fish receiving the 10.0 or 50.0 mg/kg dose. In contrast, b oth splenic weight and splenic total cellularity increased proportionately with the increase in the drug dosage. Histopathologic examination of the sp leens showed normal patterns for both control and 10.0 mg/kg dose groups. A t 50.0 mg/kg, spleens were characterized by marked expansion of the white p ulp, although lymphocytes were rare. Melanomacrophage centers at the higher dose were also larger and more numerous than in the control group. Evaluat ion of splenic and pronephric leukocytes with apoptotic markers showed an i ncrease in apoptotic cells in the pronephros with increasing drug dose. The se changes in fish are consistent with those seen in humans and laboratory rodents dosed with azathioprine, suggesting that fish may be potentially us eful as preliminary models for detecting immunosuppressive compounds. (C) 1 999 Elsevier Science B.V. All rights reserved.