Tumor necrosis factor-α production and disease severity after immunization with enriched major core protein (p26) and/or infection with equine infectious anemia virus

Cardinal features of equine infectious anemia (EIA) include fever, hemolytic anemia and thrombocytopenia during the acute phase of the disease, and cachexia and anemia seen during the chronic phase. These signs are thought to result from the release of inflammatory cytokines such as TNF-α. In order to determine if TNF-α has a role in the pathogenesis of acute EIA and vaccine-induced disease enhancement, we measured plasma concentrations of TNF-α in ponies immunized with virus enriched major core protein-p26 and/or experimentally infected with EIAV. Naturally infected inapparent EIAV carriers were also studied. TNF-α levels were determined by means of a WEHI 164, clone 13 cytotoxicity assay. We show a significant positive temporal correlation between TNF-α levels, severity of symptoms (fever and thrombocytopenia) and viremia. Furthermore, TNF-α levels also correlate with strain virulence and the disease enhancement seen in vaccinated ponies. Of this group of animals, those challenged with a heterologous virulent strain presented the most unfavorable outcome as well as the highest levels of TNF-α and viremia. The TNF-α activity observed in the bioassay was completely abrogated by a polyclonal rabbit anti-human TNF-α antiserum, thus confirming the specificity of the plasma cytotoxicity. Our observations indicate that TNF-α production correlates with the outcome of infection with EIAV.