| Abstract | IL-6 is known to be an important pro- and anti-inflammatory cytokine, which is up-regulated during sepsis. Our previous work has suggested a role for IL-6 in the up-regulation of C5aR in sepsis. We reported earlier that interception of C5a or C5aR results in improved outcomes in experimental sepsis. Using the cecal ligation/puncture (CLP) model in mice, we now demonstrate that treatment with anti-IL-6 Ab (anti-IL-6) results in significantly improved survival, dependent on the amount of Ab infused. CLP animals showed significantly increased binding of 125I-labeled anti-C5aR to organs when compared to either control mice at 0 h or CLP animals infused with normal rabbit 125I-labeled IgG. Binding of 125I-labeled anti-C5aR to lung, liver, kidney, and heart was significantly decreased in anti-IL-6-treated animals 6 h after CLP. RT-PCR experiments with mRNA isolated from various organs obtained 3, 6, and 12 h after CLP demonstrated increased C5aR mRNA expression during the onset of sepsis, which was greatly suppressed in CLP mice treated with anti-IL-6. These data suggest that IL-6 plays an important role in the increased expression of C5aR in lung, liver, kidney, and heart during the development of sepsis in mice and that interception of IL-6 leads to reduced expression of C5aR and improved survival. |
| Authors | Niels C Riedemann, Thomas A Neff, Ren-Feng Guo, Kurt D Bernacki, Ines J Laudes, J Vidya Sarma, John D Lambris, Peter A Ward
(Affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.)
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| Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 170
Issue 1
Pg. 503-7
(Jan 1 2003)
ISSN: 0022-1767 United States |
| PMID | 12496437
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Antibodies, Blocking
- Antibodies, Monoclonal
- Antigens, CD
- Binding Sites, Antibody
- Immunosuppressive Agents
- Interleukin-6
- RNA, Messenger
- Receptor, Anaphylatoxin C5a
- Receptors, Complement
- Complement C5a
|
| Topics |
- Amino Acid Sequence
- Animals
- Antibodies, Blocking
(therapeutic use)
- Antibodies, Monoclonal
(therapeutic use)
- Antigens, CD
(biosynthesis, genetics, immunology)
- Binding Sites, Antibody
- Cecum
- Complement C5a
(metabolism)
- Down-Regulation
(immunology)
- Immunosuppressive Agents
(therapeutic use)
- Interleukin-6
(antagonists & inhibitors, blood, immunology)
- Kidney
(immunology, metabolism)
- Ligation
- Liver
(immunology, metabolism)
- Lung
(immunology, metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Molecular Sequence Data
- Myocardium
(immunology, metabolism)
- Punctures
- RNA, Messenger
(antagonists & inhibitors)
- Receptor, Anaphylatoxin C5a
- Receptors, Complement
(antagonists & inhibitors, biosynthesis, genetics, immunology)
- Sepsis
(immunology, mortality, therapy)
- Survival Analysis
|
