SUPPRESSION OF MEGAKARYOCYTE COLONY GROWTH BY PLASMA FROM FOALS INFECTED WITH EQUINE INFECTIOUS-ANEMIA VIRUS

Foals infected with equine infectious anemia virus become thromhocytop enic 7 to 20 days after virus inoculation, and within a few days follo wing the onset of detectable viremia. The thrombocytopenia is associat ed with suppression of platelet production, Possible mediators of supp ression of thrombopoiesis include tumor necrosis factor-alpha (TNF-alp ha) and transforming growth factor-beta (TGF-beta), cytokines that are released during inflammation, To assess effects of plasma or serum fr om infected foals on megakaryocyte (MK) growth and maturation in vitro , equine low-density hone marrow cells were cultured for clonogenic an d ploidy assays. Neutralizing antibodies to TNF-alpha and TGF-beta wer e added to cultures to determine the contribution of these cytokines t o suppression of thrombopoiesis. Plasma from the immediately pre-throm bocytopenia (Pre-Tp) period significantly reduced MK colony numbers. T his suppression was partially reversed upon antibody neutralization of plasma TNF-alpha, TGF-beta, or both. There were no differences in plo idy distribution of MK grown in the presence of preinfection serum com pared with those grown in the presence of Pre-Tp serum, These results indicate that TNF-alpha and TGF-beta may contribute to suppression of MK proliferation and represent likely factors in the pathogenesis of t hrombocytopenia. (C) 1997 by The American Society of Hematology.