title: The role for host-immune factors in the in vivo antiviral effects of tumour necrosis factor.
abstract: This report examines the host-immune response to vaccinia virus in mice exposed to tumour necrosis factor (TNF). Exposure to TNF was done via two approaches; (1) mice were treated with TNF in complex with a specific anti-TNF antibody (Ab 301) which enhances the antiviral efficacy of this cytokine, prior to vaccinia virus (VV) infection; and (2) mice were infected with a recombinant VV which encodes the murine TNF gene (VV-HA-TNF). The antiviral effect induced by TNF plus Ab 301 in CBA/H mice was not sensitive to sub-lethal gamma irradiation, indicating that a proliferative immune cell population was not responsible for the observed attenuated VV growth. This was further evidenced by NK cell and CTL studies which showed, when compared to controls, that TNF plus Ab 301 treated animals had decreased spleen NK cell and CTL activities. This suggests that a non-specific factor, effective earlier than day 2 postinfection, was responsible for the restriction of VV growth. To further investigate this possibility, mice were treated with either the TNF/Ab 301 regimen, or infected with VV-HA-TNF, and their peritoneal exudate cells (PEC) examined during early VV infection. Control recombinant VV infection resulted in an increase in neutrophil numbers, and TNF/Ab 301 treatment before infection did not increase this further. VV-HA-TNF infection of mice, however, induced a massive but transient increase in the number of neutrophils, suggesting that this cell population was important to the in vivo restriction of VV-HA-TNF growth.
authors.affiliation: Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT.
authors.forename: B A
authors.initials: BA
authors.lastname: Lidbury
authors.forename: I A
authors.initials: IA
authors.lastname: Ramshaw
authors.forename: S K
authors.initials: SK
authors.lastname: Sambhi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins / Q000494:pharmacology; D011995:Recombination, Genetic; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*; D014615:Vaccinia / Q000276:immunology*; D014616:Vaccinia virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma