TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION AND DISEASE SEVERITY AFTER IMMUNIZATION WITH ENRICHED MAJOR CORE PROTEIN (P26) AND OR INFECTION WITHEQUINE INFECTIOUS-ANEMIA VIRUS/

Cardinal features of equine infectious anemia (EIA) include fever, hem olytic anemia and thrombocytopenia during the acute phase of the disea se, and cachexia and anemia seen during the chronic phase. These signs are thought to result from the release of inflammatory cytokines such as TNF-alpha. Zn order to determine if TNF-alpha has a role in the pa thogenesis of acute EIA and vaccine-induced disease enhancement, we me asured plasma concentrations of TNF-alpha in ponies immunized with vir us enriched major core protein-p26 and/or experimentally infected with EIAV. Naturally infected inapparent EIAV carriers were also studied. TNF-alpha levels were determined by means of a WEHI 164, clone 13 cyto toxicity assay. We show a significant positive temporal correlation be tween TNF-alpha levels, severity of symptoms (fever and thrombocytopen ia) and viremia. Furthermore, TNF-alpha levels also correlate with str ain virulence and the disease enhancement seen in vaccinated ponies. O f this group of animals, those challenged with a heterologous virulent strain presented the most unfavorable outcome as well as the highest levels of TNF-alpha and viremia. The TNF-alpha activity observed in th e bioassay was completely abrogated by a polyclonal rabbit anti-human TNF-alpha antiserum, thus confirming the specificity of the plasma cyt otoxicity. Our observations indicate that TNF-alpha production correla tes with the outcome of infection with EIAV. (C) 1997 Elsevier Science B.V.