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Interleukin-6 Promotes Murine Estrogen Deficiency-Associated Cerebral Aneurysm Rupture.

Daisuke Wajima1,2, Siham Hourani1, William Dodd1

  • 1Department of Neurosurgery, University of Florida, Gainesville, Florida.

Neurosurgery
|July 3, 2019
PubMed
Summary
This summary is machine-generated.

Estrogen deficiency increases cerebral aneurysm rupture risk. Interleukin-6 (IL-6) inhibition significantly reduced rupture rates in estrogen-deficient mice by decreasing macrophage infiltration.

Keywords:
Aneurysm ruptureCerebral aneurysmEstrogen deficiencyIL-6 (interleukin 6)Murine aneurysm mode

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Area of Science:

  • Neuroscience
  • Immunology
  • Endocrinology

Background:

  • Estrogen deficiency is linked to increased cerebral aneurysm rupture.
  • The underlying mechanisms remain largely unknown.
  • Interleukin-6 (IL-6) is investigated as a potential mediator.

Purpose of the Study:

  • To determine if IL-6 is required for increased cerebral aneurysm rupture in estrogen-deficient states.
  • To investigate the role of IL-6 in macrophage infiltration in the context of estrogen deficiency and aneurysm rupture.

Main Methods:

  • IL-6 expression was analyzed in human cerebral aneurysms.
  • Cerebral aneurysms were induced in estrogen-deficient mice (VCD or ovariectomy).
  • Mice received either an IL-6 receptor (IL-6R) neutralizing antibody or a control IgG, followed by assessment of aneurysm rupture and macrophage infiltration.

Main Results:

  • IL-6 was expressed in human cerebral aneurysms but not control arteries.
  • Serum IL-6 levels were elevated in ovariectomized mice.
  • Selective IL-6R inhibition significantly suppressed aneurysm rupture in estrogen-deficient mice (VCD: 31.6% vs 70.0%; OVE: 28.6% vs 65.2%).
  • IL-6R inhibition reduced macrophage infiltration at the circle of Willis (1.9 vs 5.7 cells/2500 μm²).

Conclusions:

  • Elevated IL-6 in estrogen deficiency promotes cerebral aneurysm rupture through enhanced macrophage infiltration.
  • Inhibiting IL-6 signaling via IL-6R neutralization effectively reduces aneurysm rupture in estrogen-deficient mice.
  • IL-6R inhibition did not affect aneurysm formation or rupture in wild-type mice, suggesting a specific role in estrogen-deficient conditions.