Journal article
Interleukin‐10 Suppresses Sympatho‐Excitatory Responses to Central LPS in Rats
The FASEB journal, Vol.21(6), pp.A884-A884
2007
DOI: 10.1096/fasebj.21.6.A884-c
Abstract
The role of the anti‐inflammatory cytokine interleukin (IL)‐10 in counteracting endotoxin (LPS)‐induced acute phase sympatho‐excitatory responses has not been studied. In male rats, adenoviral vectors encoding human IL‐10 (ADIL10, 30 μL; 3x1010 plaque‐forming units) or β‐galactosidase (βGal) were injected into the lateral ventricle. One week later, under anesthesia, renal sympathetic nerve activity (RSNA, %Δ), mean arterial pressure (MAP, ΔmmHg) and heart rate (HR, Δbpm) were recorded during intracerebroventricular (ICV) of LPS (4 μg). Cerebrospinal fluid (CSF) and hypothalamic tissue were collected 4 hr after LPS injection. Abundant gene expression of ADIL10 mRNA was detected by RT‐PCR in the hypothalamus after ADIL10 (n=4) but not βGal (n=4). After ADIL10, LPS elicited significantly (∗p<0.05, vs βGal, n=5) smaller increases in RSNA (26.6 ± 7.8∗ vs 50.2 ± 8.4), HR (33.6 ± 12.2∗ vs 91.6 ± 10.7), MAP (4.4 ± 2.4∗ vs 15.7 ± 3.6), hypothalamic cyclooxygenase‐2 (COX‐2) mRNA (0.09 ± 0.01∗ vs 0.17 ± 0.02; real‐time PCR, normalized to GAPDH mRNA) and CSF prostaglandin E2 (PGE2) (466 ± 78∗ vs 1078 ±153 pg/ml; ELISA). Acute ICV injection of IL‐10 (0.5 μg, n=5) 5–10 min prior to ICV LPS resulted in similar significant reductions in RSNA, HR, MAP, hypothalamic COX‐2 mRNA and CSF PGE2, sampled 4 hr later. ICV NS398 (2 μg, n=5), a specific COX‐2 inhibitor, also blocked LPS‐induced sympatho‐excitatory responses. We conclude that IL‐10 has a potent inhibitory influence on central neural mechanisms regulating sympathetic drive, and may have therapeutic potential in the treatment of cardiovascular diseases with an inflammatory component.
Supported by NIH HL‐073986.
Details
- Title: Subtitle
- Interleukin‐10 Suppresses Sympatho‐Excitatory Responses to Central LPS in Rats
- Creators
- Zhi‐Hua Zhang - University of IowaYang Yu - University of IowaShun‐Guang Wei - University of IowaRobert B Felder - Veterans Affairs Medical Center
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.21(6), pp.A884-A884
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.21.6.A884-c
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- NIH (HL‐073986)
- Language
- English
- Date published
- 2007
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984071630102771
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