Multiplex analysis of cytokines in the blood of cynomolgus macaques naturally infected with Ebola virus (Reston serotype).
Ebola virus (EBO) causes the most severe form of viral hemorrhagic fever in humans and nonhuman primates with up to 90% of infections culminating in death. The requirement of maximum containment laboratories for Ebola virus research has limited opportunities to study the pathogenesis of EBO infections. While tissue damage does occur, often it would appear not to be sufficient to explain death, indicating that soluble mediators play an important role in disease progression. In previous studies, fatal human infections with the Zaire subtype of Ebola (EBO-Z) were associated with an increase in the levels of inflammatory cytokines. In this investigation, a new multiplex assay was developed and used to measure circulating levels of cytokines and chemokines in cynomolgus macaques infected with the Reston subtype of EBO (EBO-R). Increased levels of IL-6, TNF-alpha, IFN-gamma, IL-2, IL-4, IL-8, IL-10, and GM-CSF were detected in infected animals, and the increase in circulating cytokines correlated with an increase in circulating viral antigen. Blood samples from animals showing high levels of cytokines were also tested for the chemokines: MCP-1, IL-1beta, MIP-1alpha, MIP-1beta, IP-10, and RANTES. High levels of MCP-1 and MIP-1beta, and RANTES were found in infected primates and, while levels were more variable, IL-1beta was detected only in infected animals.
Hutchinson
K L
KL
Special Pathogens Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mail stop G14, Atlanta, GA 30333, USA. khutchinson@cdc.gov
Villinger
F
F
Miranda
M E
ME
Ksiazek
T G
TG
Peters
C J
CJ
Rollin
P E
PE
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000097:blood; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D029043:Ebolavirus / Q000276:immunology* / Q000302:isolation & purification; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000737:chemistry / Q000235:genetics; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000276:immunology* / Q000821:virology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor