Lethal Staphylococcus aureus-induced shock in primates: prevention of death with anti-TNF antibody.
A successful experimental treatment for gram-positive sepsis to our knowledge has not been achieved. The objectives of this study were to develop a nonhuman primate model of lethal gram-positive sepsis employing the micro-organism Staphylococcus aureus and to determine the efficacy of treatment using monoclonal antibody (MAb) to tumor necrosis factor alpha (TNF). The antibody was administered intravenously, 15 mg/kg, 30 minutes after the beginning of a 2-hour infusion of S. aureus, 4 x 10(10) colony forming units/kilogram. The baboons infused with S. aureus demonstrated the release of the cytokines TNF and interleukin-6 (IL-6), but endotoxin was not observed in the plasma at any time. Treatment with antibody to TNF abolished the rise in serum TNF levels and reduced the increased levels of IL-6. Treatment with MAb to TNF prevented multiple organ failure and achieved permanent (> 7 day) survival of all baboons.
Hinshaw
L B
LB
Oklahoma Medical Research Foundation, Oklahoma City 73104.
Emerson
T E
TE
Taylor
F B
FB
Chang
A C
AC
Duerr
M
M
Peer
G T
GT
Flournoy
D J
DJ
White
G L
GL
Kosanke
S D
SD
Murray
C K
CK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001777:Blood Coagulation; D015169:Colony Count, Microbial; D015850:Interleukin-6 / Q000097:blood; D010215:Papio; D012772:Shock, Septic / Q000276:immunology / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D013203:Staphylococcal Infections / Q000150:complications* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha