Faculty Collaboration Database

IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia. J Endotoxin Res 2002;8(1):59-67

Date

05/01/2002

Pubmed ID

11981446

DOI

10.1177/09680519020080010601

Scopus ID

2-s2.0-0036123008 (requires institutional sign-in at Scopus site)   80 Citations

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.

Author List

Calkins CM, Bensard DD, Shames BD, Pulido EJ, Abraham E, Fernandez N, Meng X, Dinarello CA, McIntyre RC Jr

Author

Casey Matthew Calkins MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Chemokine CXCL1
Chemokine CXCL2
Chemokines, CXC
Chemotactic Factors
Disease Models, Animal
Endotoxemia
Growth Substances
Humans
Intercellular Signaling Peptides and Proteins
Interleukin 1 Receptor Antagonist Protein
Lipopolysaccharides
Liver
Lung
Male
Monokines
Neutrophil Infiltration
Neutrophils
Peroxidase
RNA, Messenger
Rats
Rats, Sprague-Dawley
Receptors, Interleukin-1
Recombinant Proteins
Salmonella typhimurium
Sialoglycoproteins