Journal article
Central gene transfer of Interleukin-10 reduces hypothalamic inflammation and evidence of heart failure in rats after Myocardial Infarction
Circulation research, Vol.101(3), pp.304-312
2007
DOI: 10.1161/CIRCRESAHA.107.148940
PMID: 17569888
Abstract
The expression of proinflammatory cytokines increases in hypothalamus of rats with myocardial infarction (MI) and heart failure. We used central gene transfer of human interleukin (IL)-10, a potent antiinflammatory cytokine, to counter the effects of brain proinflammatory cytokines and examine their functional significance. Sprague–Dawley rats underwent coronary ligation to induce MI or sham surgery (SHAM). One week later, adenoviral vectors encoding human IL-10 (AdIL-10) or β-galactosidase (βGal) were injected (30 μL over 30 minutes) into lateral ventricle. One week after injection, there was abundant expression of human IL-10 in the brain of MI+AdIL-10 and SHAM+AdIL-10 rats. Compared with SHAM+βGal, MI+βGal had increased (P<0.05) IL-1β and cyclooxygenase-2 mRNA and protein and nuclear factor κB activity in the hypothalamus, cyclooxygenase-2 fluorescence in perivascular cells of the paraventricular nucleus of hypothalamus, prostaglandin E2 in cerebrospinal fluid, and Fra-like activity (indicating neuronal excitation) in paraventricular nucleus. Plasma norepinephrine levels, lung/body weight, right ventricle/body weight, and left ventricular end-diastolic pressure were increased and maximal left ventricular dP/dt was decreased. All of these findings were ameliorated in MI rats treated with AdIL-10. Hypothalamic tumor necrosis factor-α and circulating tumor necrosis factor-α and IL-1β levels, also increased in MI+βGal, were not affected by AdIL-10 treatment. Rat native IL-10 was not affected by MI or AdIL-10. AdIL-10 had no effects on SHAM rats. The results demonstrate that cardiovascular and autonomic mechanisms leading to heart failure after MI can be modulated by manipulating the balance between proinflammatory and antiinflammatory cytokines in the brain.
Details
- Title: Subtitle
- Central gene transfer of Interleukin-10 reduces hypothalamic inflammation and evidence of heart failure in rats after Myocardial Infarction
- Creators
- Yang Yu - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesZhi-Hua ZHANG - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesShun-Guang WEI - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesYi Chu - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesRobert M WEISS - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesDonald D HEISTAD - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesRobert B FELDER - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.101(3), pp.304-312
- DOI
- 10.1161/CIRCRESAHA.107.148940
- PMID
- 17569888
- NLM abbreviation
- Circ Res
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Publisher
- Lippincott; Hagerstown, MD
- Language
- English
- Date published
- 2007
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040269002771
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