| Title | IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia. | | Author(s) | Calkins CM, Bensard DD, Shames BD, Pulido EJ, Abraham E, Fernandez N, Meng X, Dinarello CA, McIntyre RC | | Institution | Department of Surgery, University of Colorado Health Sciences Center and Veterans Affairs Hospital, 4200 East 9th Avenue, Box C-313, Denver, CO 80262, USA. | | Source | J Endotoxin Res 2002; 8(1):59-67. | | MeSH | Animals
Chemokines, CXC
Chemotactic Factors
Disease Models, Animal
Endotoxemia
Growth Substances
Humans
Intercellular Signaling Peptides and Proteins
Lipopolysaccharides
Liver
Lung
Male
Monokines
Neutrophil Infiltration
Neutrophils
Peroxidase
RNA, Messenger
Rats
Rats, Sprague-Dawley
Receptors, Interleukin-1
Recombinant Proteins
Research Support, U.S. Gov't, P.H.S.
Salmonella typhimurium
Sialoglycoproteins
| | Abstract | The influx of neutrophils into tissues in response to inflammatory stimuli involves C-X-C chemokines. Interleukin-1 (IL-1) stimulates chemokine production in vitro, but its role in vivo on chemokine production is not as clearly understood. We hypothesized that IL-1 mediates in vivo tissue C-X-C chemokine production induced by systemic lipopolysaccharide (LPS). IL-1 activity was blocked by IL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella typhi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of organ injury were measured. LPS administration resulted in increased plasma, lung, and liver IL-1beta that was decreased by Il-1Ra. LPS also induced an increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However, IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein expression in the liver (45% decrease) and MIP-2 protein expression in plasma (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS- treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC-1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil accumulation, respectively, following LPS. In addition, indices of both lung and liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS induces IL-1beta and MIP-2 expression in the lung and liver, both of which are IL-1 dependent. Although lung neutrophil accumulation in both lung and liver after LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These data suggest that IL-1 regulates tissue chemokine expression and neutrophil accumulation after LPS. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 11981446 |
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