Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2364-2367
© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Interleukin-6 Exacerbates Early Atherosclerosis in Mice
From the Departments of Pathology (S.A.H., P.S., N.H., R.T.), Medicine (D.C.), and Biochemistry (R.T.), University of Vermont, Burlington, VT 05405.
Correspondence to Sally Ann Huber, PhD, Department of Pathology, University of Vermont, 55A South Park Drive, Colchester, VT 05446. E-mail shuber{at}salus.uvm.edu
Abstract—Acute-phase proteins,
which respond to systemic proinflammatory cytokines such as
interleuken-6, are elevated in cardiovascular disease
and are predictive markers of future ischemic events, even over
decades. This suggests a role for proinflammatory cytokines
and/or acute phase proteins in early lesion development. To explore
this issue, we fed C57Bl/6 and nonobese diabetic male mice high-fat
(20% total fat, 1.5% cholesterol) diets and
ApoE-deficient male mice both high-fat and normal chow diets for 6 to
21 weeks, injecting them weekly with either 5000 U recombinant
interleukin-6 (rIL-6) or saline buffer. Blood was collected when
animals were euthanized and assayed for cytokines, acute-phase
proteins, and cholesterol. Across all mice, IL-6 injection
resulted in significant increases in proinflammatory cytokines
(IL-6, 4.6-fold; IL-1ß, 1.6-fold; and tissue necrosis factor-
,
1.7-fold) and fibrinogen (1.2-fold) and with decreased concentrations
of albumin (0.9-fold) in plasma. Total cholesterol
levels were unchanged between rIL-6–treated and nontreated groups.
Serial sections through the aortic sinus were stained with oil red O to
detect fatty streaks, and area of the lesions was determined by image
analysis. Although no fatty streaks were detected in the
nonobese diabetic mice with or without rIL-6 treatment, rIL-6 treatment
increased lesion size in C57Bl/6 and ApoE-deficient mice 1.9- to
5.1-fold over lesions in saline-treated animals. These results suggest
that under the appropriate circumstances changes in circulating
proinflammatory cytokines and acute-phase proteins may be more
than just markers of atherosclerosis but actual
participants in early lesion development.
Key Words: inflammation • atherosclerosis • interleukin-6
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