Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection.
Here we describe a lethal mouse model infected with dengue virus type 2 with several similarities to human DEN-2 infection. Clinically animals demonstrated anemia, thrombocytopenia, pre-terminal paralysis and shock. The most impressive changes were seen with tumor necrosis factor (TNF)-alpha, which abruptly and steeply increased 24 h before the exitus (mean at day 6). Serum levels of IL-1beta, IL-6, IL-10, IL-1 receptor antagonist and soluble TNF receptor I continuously increased during the time of infection. A 100% mortality rate was noted in that group of animals. Treating animals with anti-TNF-alpha serum reduced mortality rate down to 40% (P<0.05). Our model supports the view that activation of innate immune response is at least partially responsible for mortality in DEN-2 infection, and in line with this concept, anti-TNF treatment significantly reduces mortality rates.
Atrasheuskaya
Alena
A
State Research Center of Virology and Biotechnology Vector, Novosibirsk region, Russia.
Petzelbauer
Peter
P
Fredeking
Terry M
TM
Ignatyev
George
G
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000627:therapeutic use*; D003715:Dengue / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D003716:Dengue Virus / Q000276:immunology / Q000472:pathogenicity; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000914:Antibodies, Viral; D014409:Tumor Necrosis Factor-alpha