Effects of intravenous IL-8 administration in nonhuman primates.
IL-8, a cytokine known for its potent and specific neutrophil activation and chemoattractant properties, has been recently detected in the circulation during septic shock, endotoxemia, and after IL-1 alpha administration. Because of its observed in vitro actions, it has been hypothesized that IL-8 may contribute to the dynamics of circulating granulocytes and to the pathologic sequelae seen in sepsis. Here, human rIL-8 is administered to healthy nonhuman primates as a single i.v. injection or as a continuous 8-h i.v. infusion. We demonstrate that both methods of i.v. administration result in a rapid but transient, severe granulocytopenia, followed by a granulocytosis that persists as long as IL-8 levels are detectable in the circulation. There were no hemodynamic changes after IL-8 administration, and animals remained clinically stable during the 24-h observation period. No detectable circulating TNF-alpha, IL-1 beta, or IL-6 response was induced by either IL-8 administration regimen. Histopathologic examination revealed mild to moderate neutrophilic margination in lung, liver, and spleen, of greater severity in baboons receiving the 8-h infusion. There was no associated neutrophilic infiltration or tissue injury. Thus, IL-8 modulates circulating granulocyte dynamics and likely directs their actions, but when administered i.v. to healthy animals, either as a bolus dose or as a continuous infusion for up to 8 h, does not induce the hemodynamic and metabolic aberrations or the acute organ damage seen during sepsis.
Van Zee
K J
KJ
Laboratory of Surgical Metabolism, Cornell University Medical College, New York, NY 10021.
Fischer
E
E
Hawes
A S
AS
Hébert
C A
CA
Terrell
T G
TG
Baker
J B
JB
Lowry
S F
SF
Moldawer
L L
LL
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D016209:Interleukin-8 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007958:Leukocyte Count / Q000187:drug effects; D010215:Papio; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D018805:Sepsis / Q000503:physiopathology; D013154:Spleen / Q000166:cytology
D016207:Cytokines; D016209:Interleukin-8; D011994:Recombinant Proteins