Cerebral vasomotor responses after recombinant interleukin 2 infusion.
The effects of systemic human recombinant interleukin 2 (rIL-2) infusion upon both the vasoconstrictor effect of hypocapnia and the endothelium-dependent vasodilator effect of acetylcholine (Ach) were examined in anesthetized rats equipped with cranial windows. Prior to the functional studies, each of six animals received an i.v. infusion of rIL-2 (6 x 10(5) IU/kg) every 8 h for 3 days. At the same time, six control animals received infusions of equivalent volumes of sterile water. Eight h after the final infusion, each animal was anesthetized and equipped with a cranial window for the observation of pial arterioles overlying the left frontoparietal cortex. Pial arteriolar diameters were measured before and after the topical application of Ach which in normal cerebral arterioles elicits the release of endothelium-dependent relaxing factor, causing vasodilation. When arteriolar diameters returned to base line, they were measured again both before and during hyperventilation-induced hypocapnia. Following functional assessments, these same pial vessels were processed for study by transmission electron microscopy to determine if any observed functional changes correlated with morphological abnormality. Results of the statistical analyses suggested that normal Ach-induced endothelium-dependent vasodilation was absent in the rIL-2-infused group. Additionally, these animals exhibited reduced reactivity to the vasoconstrictive effects of arterial hypocapnia. The control group exhibited normal responsiveness to both Ach and hyperventilation. Ultrastructural studies revealed occasional morphological alterations of both vascular smooth muscle and endothelial cells in some vessels of rIL-2-infused animals but not in controls. These data suggest that repeated systemic rIL-2 infusion results in altered vasomotor responsiveness within the cerebral microcirculation. The data also suggest that the observed vasomotor changes are not always accompanied by overt morphological alterations of either endothelial or smooth muscle cells.
Ellison
M D
MD
Department of Anatomy, Medical College of Virginia, Richmond 23298-0709.
Krieg
R J
RJ
Merchant
R E
RE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D014661:Vasoconstriction / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D007376:Interleukin-2; D011994:Recombinant Proteins; D000109:Acetylcholine