Mechanisms of Inflammatory Liver Injury

Liver Diseases Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00011284
• Other study ID #: 6091-CP-001
• Status: Completed
• Phase: N/A
• First received: February 15, 2001
• Last updated: June 23, 2005
• Est. completion date: November 2001

Study information

• Verified date: September 2002
• Source: National Institute of Environmental Health Sciences (NIEHS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

White blood cells can cause liver damage if they inappropriately accumulate in the liver in large numbers. Such an event can occur if an individual's blood is exposed to endotoxin, a substance released from the cell walls of many species of bacteria. The purpose of this study is to isolate neutrophils, an important white blood cell, from the blood of normal volunteers, and put them in tissue culture with isolated liver cells. The experiments will determine how endotoxin can increase the ability of neutrophils to damage liver cells. All studies supported by this grant will be done with isolated cells in tissue culture. This experimental model will reveal possible mechanisms that can in the future be evaluated in human diseases such as bacterial sepsis.

Description:

Neutrophils will be isolated from normal human volunteers and placed in cell culture with isolated hepatocytes or C3A cells (hepatoblastoma cell line that exhibit many characteristics of normal hepatocytes). These experiments will evaluate the mechanisms by which neutrophil adhere to the surface of hepatocytes, and the mechanisms by which the attached neutrophils can damage or kill the hepatocytes. Mechanisms of adhesion will involve understanding of the chemokines released by the hepatocytes that stimulate neutrophil adhesiveness, the cytokines that activate hepatocytes to express chemokines and adhesion molecules, the adhesion receptors on the neutrophil surface that are able to recognize the adhesion molecules on the hepatocyte surface, and the ability of adhesion to enhance and focus cytotoxic chemicals coming from the stimulated neutrophils. In addition, the role endotoxin can play in these sequence of events is being studies, and the specific cytotoxic mechanisms released by the neutrophils are under study. As noted in the brief summary, this grant only supports use of human cells in vitro (i.e., all experiments will be done in tissue culture). The purpose of working with this experimental model is to define what mechanisms should in future experiments be evaluated in patients with endotoxin induced disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 2001
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 65 Years
• Eligibility: Only blood from normal subjects will be used in the in vitro experiments.

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Liver Diseases

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Environmental Health Sciences (NIEHS)

Country where clinical trial is conducted

United States,