PMID- 17569888
OWN - NLM
STAT- MEDLINE
DCOM- 20070914
LR  - 20161124
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 101
IP  - 3
DP  - 2007 Aug 3
TI  - Central gene transfer of interleukin-10 reduces hypothalamic inflammation and 
      evidence of heart failure in rats after myocardial infarction.
PG  - 304-12
AB  - 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 beta-galactosidase (betaGal) were injected (30 microL 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+betaGal, MI+betaGal had increased (P<0.05) IL-1beta and 
      cyclooxygenase-2 mRNA and protein and nuclear factor kappaB activity in the 
      hypothalamus, cyclooxygenase-2 fluorescence in perivascular cells of the 
      paraventricular nucleus of hypothalamus, prostaglandin E(2) 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-alpha and 
      circulating tumor necrosis factor-alpha and IL-1beta levels, also increased in 
      MI+betaGal, 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.
FAU - Yu, Yang
AU  - Yu Y
AD  - Department of Internal Medicine, Roy J. and Lucille A. Carver College of 
      Medicine, University of Iowa, Iowa City, IA 52242, USA.
FAU - Zhang, Zhi-Hua
AU  - Zhang ZH
FAU - Wei, Shun-Guang
AU  - Wei SG
FAU - Chu, Yi
AU  - Chu Y
FAU - Weiss, Robert M
AU  - Weiss RM
FAU - Heistad, Donald D
AU  - Heistad DD
FAU - Felder, Robert B
AU  - Felder RB
LA  - eng
GR  - R01 HL-073986/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070614
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Cytokines)
RN  - 0 (IL10 protein, human)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Ptgs2 protein, rat)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
CIN - Circ Res. 2007 Aug 3;101(3):221-3. PMID: 17673679
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Brain
MH  - Cyclooxygenase 2/biosynthesis/genetics
MH  - Cytokines/biosynthesis/genetics
MH  - Dinoprostone/biosynthesis/cerebrospinal fluid
MH  - Disease Progression
MH  - Gene Transfer Techniques
MH  - Genetic Vectors/administration & dosage/*therapeutic use
MH  - Heart Failure/diagnostic imaging/etiology/physiopathology/*prevention & control
MH  - Heart Ventricles/pathology
MH  - Injections
MH  - Interleukin-10/genetics/*physiology
MH  - Interleukin-1beta/biosynthesis/genetics
MH  - Ligation
MH  - Lung/pathology
MH  - Male
MH  - Myocardial Infarction/*complications
MH  - NF-kappa B/metabolism
MH  - Norepinephrine/blood
MH  - Organ Size
MH  - Paraventricular Hypothalamic Nucleus/metabolism/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Fusion Proteins/genetics/physiology
MH  - Sympathetic Nervous System/*physiopathology
MH  - Tumor Necrosis Factor-alpha/biosynthesis/genetics
MH  - Ultrasonography
MH  - Ventricular Remodeling
EDAT- 2007/06/16 09:00
MHDA- 2007/09/15 09:00
CRDT- 2007/06/16 09:00
PHST- 2007/06/16 09:00 [pubmed]
PHST- 2007/09/15 09:00 [medline]
PHST- 2007/06/16 09:00 [entrez]
AID - CIRCRESAHA.107.148940 [pii]
AID - 10.1161/CIRCRESAHA.107.148940 [doi]
PST - ppublish
SO  - Circ Res. 2007 Aug 3;101(3):304-12. doi: 10.1161/CIRCRESAHA.107.148940. Epub 2007 
      Jun 14.