EVIDENCE FOR ACTIVATION OF THE SYMPATHETIC NERVOUS-SYSTEM BY RECOMBINANT HUMAN INTERLEUKIN-1-BETA IN HUMANS

Administration of interleukin-1beta (IL-1beta) 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-1beta 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-1beta. 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-1beta 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-1beta administration in humans are most likely the result of adrenergic stimulation possibly through its effect on the central nervous system.