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Cerebral vasomotor responses after recombinant interleukin 2 infusion
M D Ellison1, R J Krieg, R E Merchant
1Department of Anatomy, Medical College of Virginia, Richmond 23298-0709.
Cancer Research
|July 15, 1990
Summary
Systemic human recombinant interleukin 2 (rIL-2) infusions impaired cerebral vasodilation and vasoconstriction responses in rats. These functional changes in cerebral microcirculation occurred without consistent morphological abnormalities.
Area of Science:
- Neuroscience
- Immunology
- Vascular Biology
Background:
- Interleukin-2 (IL-2) is a cytokine with significant roles in immune responses.
- Systemic administration of IL-2 can have widespread physiological effects.
- Cerebral microcirculation plays a critical role in brain function and is regulated by vasomotor responses.
Purpose of the Study:
- To investigate the impact of systemic human recombinant interleukin-2 (rIL-2) infusion on cerebral vasomotor responsiveness.
- To assess the effects of rIL-2 on endothelium-dependent vasodilation induced by acetylcholine (Ach).
- To evaluate the influence of rIL-2 on the vasoconstrictor response to hypocapnia in cerebral arterioles.
Main Methods:
- Anesthetized rats received systemic infusions of rIL-2 or sterile water (control) for 3 days.
- Cerebral pial arterioles were observed using cranial windows.
- Vasomotor responses to topical Ach and hyperventilation-induced hypocapnia were measured.
- Vessels were examined using transmission electron microscopy for morphological changes.
Main Results:
- rIL-2 infusion abolished Ach-induced endothelium-dependent vasodilation in pial arterioles.
- Animals treated with rIL-2 showed reduced vasoconstrictive response to hypocapnia.
- Control animals exhibited normal vasomotor responses to both Ach and hypocapnia.
- Ultrastructural analysis revealed occasional morphological alterations in endothelial and smooth muscle cells of rIL-2 treated rats, but not consistently.
Conclusions:
- Repeated systemic rIL-2 infusion significantly alters vasomotor responsiveness in the cerebral microcirculation.
- The observed functional changes in cerebral blood vessels may occur without overt morphological damage.
- These findings highlight potential neurovascular side effects of systemic IL-2 therapy.