The enhancement of human tumor necrosis factor-alpha antiviral activity in vivo by monoclonal and specific polyclonal antibodies.
This report describes the potentiation of the antiviral effects of human tumour necrosis factor-alpha (TNF-alpha) in vivo by specific antibodies. Complexes of TNF with either an anti-TNF monoclonal or polyclonal antibody at optimal doses induced a significantly greater antiviral (vaccinia virus) state in CBA/H mice than TNF alone. Furthermore, an antiviral synergy between murine gamma-interferon and TNF was found in vivo when the latter was in complex with enhancing antibody. Two other inbred mouse strains, C57/B6 and BALB/c, were also examined under these conditions. These antibodies greatly increase the binding of TNF to the surface of cells, which may account for the observed enhancement of TNF activity. Such antibodies may be of value clinically in viral diseases and cancer therapy where an increase in TNF activity, in the absence of side effects, would lead to more effective use of this cytokine in human therapy.
Lidbury
B A
BA
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
Aston
R
R
Ramshaw
I A
IA
Cowden
W B
WB
Rathjen
D A
DA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000936:Antigen-Antibody Complex / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010053:Ovary / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*; D014616:Vaccinia virus / Q000187:drug effects*
D000906:Antibodies; D000936:Antigen-Antibody Complex; D000998:Antiviral Agents; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma