SYNERGISTIC EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERFERON-GAMMA ON FELINE HEMATOPOIETIC PROGENITORS

Pathogenic mechanisms that underlie feline leukaemia virus subgroup-C (FeLV-C) induced erythroid aplasia are unknown. FeLV-C infection is associated with higher serum levels of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), which may act synergistically to cause haemopoietic suppression. In the present studies, the synergistic effects of TNF-alpha and IFN-gamma on feline bone marrow progenitors in vitro were evaluated. Bone marrow mononuclear cells from specific-pathogen-free cats were exposed to TNF-alpha (100 and 200 pg/ml) and IFN-gamma (100 or 200 units/ml), alone or in combination, for 2 h before plating for clonal assays of colony forming units. Our results show that TNF-alpha and IFN-gamma in combination caused marked suppression of feline colony forming units-erythroid (CFU-E), burst forming units-erythroid (BFU-E), and colony forming units-fibroblasts (CFU-F), whereas colony forming units-granulocyte/macrophage (CFU-GM) were minimally affected. The same concentrations of TNF-alpha and IFN-gamma alone had minimal effects on CFU-E, BFU-E and CFU-F. These results suggest that TNF-alpha and IFN-gamma may play a significant role in regulating haemopoiesis in cats and may be involved in the pathogenesis of erythroid aplasia in cats infected with feline leukaemia virus.