Experimental study on the possibility of treatment of some hemorrhagic fevers.
After intracerebral challenge with 100 PFU of Lassa virus (strain Josiah), all infected mice (CBA/calac) died (control group). Production of pro-inflammatory cytokines (IL-1beta, TNF-alpha) significantly increased in the blood of these mice during the infection. For neutralization of increasing concentrations of these cytokines recombinant IL-1RA was used intraperitonealy at a dose 100 microg kg(-1), everyday, within 5 days from the third day after the challenge. Injections of IL-1RA decreased the concentration of IL-1beta and TNF-alpha and resulted in survival of all infected mice (treatment group). Marburg fever (strain Popp) caused in guinea pigs by 5 LD(50) of virus lead to the significant increase of TNF-alpha in the animal's blood and caused a lethal outcome (control group). Treatment of infected guinea pigs by IL-1RA or anti-TNF serum decreased the concentration of TNF-alpha and resulted in survival of half of the animals (treatment group). For the treatment recombinant IL-1RA was used at a dose 100 microg kg(-1), intramuscularly, everyday, within 6 days from the third day after the challenge or anti-TNF serum, intramuscularly 0.5 ml (2000 U ml(-1); 1 U of the antiserum neutralises 0.03 ng of TNF-alpha), everyday, within 6 days from the third day after the challenge.
Ignatyev
G
G
State Research Center of Virology and Biotechnology 'Vector', Novosibirsk Region, 633159, Koltsovo, Russia. ignat@vector.nsc.ru
Steinkasserer
A
A
Streltsova
M
M
Atrasheuskaya
A
A
Agafonov
A
A
Lubitz
W
W
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D007106:Immune Sera; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood; D007835:Lassa Fever / Q000097:blood / Q000188:drug therapy*; D008379:Marburg Virus Disease / Q000097:blood / Q000188:drug therapy*; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017931:DNA Primers; C507764:Il1rn protein, mouse; D007106:Immune Sera; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha