Evidence for activation of the sympathetic nervous system by recombinant human interleukin-1 beta in humans.
Administration of interleukin-1 beta (IL-1 beta) to humans initiates a cascade of metabolic, hematologic, and cardiovascular events. To investigate the role of the sympathetic nervous system in the early cardiovascular response to IL-1 beta in humans, we recorded the heart rate, blood pressure, and changes in hand vein compliance in five patients with malignant melanoma treated with a 30-min infusion of 10,000-20,000 U/kg of human recombinant IL-1 beta. All patients developed fever, chills, and marked hemodynamic changes. During or shortly after the infusion, a dramatic decrease in hand vein compliance occurred (vasoconstriction). At the time of maximum venoconstriction (35 min after the start of the IL-1 beta infusion), the mean heart rate and systolic blood pressure were significantly increased by 30 mm Hg and 31 beats/min, respectively. Venoconstriction always preceded the onset of chills by several minutes (mean of 7 min), was closely correlated with the heart rate, and could be reversed by local administration of the alpha-antagonist phentolamine, indicating involvement of catecholamines. Our study shows that cardiovascular responses that occur early after IL-1 beta administration in humans are most likely the result of adrenergic stimulation possibly through its effect on the central nervous system.
Haefeli
W E
WE
Department of Medicine, Stanford University School of Medicine, California.
Bargetzi
M J
MJ
Starnes
H F
HF
Blaschke
T F
TF
Hoffman
B B
BB
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D007262:Infusions, Intravenous; D007375:Interleukin-1 / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000503:physiopathology / Q000628:therapy; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
D007375:Interleukin-1; D011994:Recombinant Proteins