Regulation of the Release of Inflammatory Mediators From Blood Leukocytes

Healthy Volunteers Clinical Trial

Official title: Regulation of the Release of Inflammatory Mediators From Blood Leukocytes: A Comparison of Healthy Subjects, Healthy Smokers and Patients With COPD.

Status Withdrawn

Clinical Trial Summary

Chronic obstructive pulmonary disease (COPD for short) involves inflammation inside the air passages of the lungs. This inflammation might be partly responsible for the shortness of breath, cough and susceptibility to chest infections that form part of COPD. Inflammation is caused, in part, by white blood cells that are attracted from the blood into the air passages. Once inside the air passages, the white blood cells may change (or 'differentiate') and release substances that produce inflammation and attract more white cells. The hypothesis is that the lifespan of these cells may also be prolonged such that they produce more inflammatory mediators and in turn perpetuate inflammation. The cycle of inflammation may damage the lungs, so we want to see what mediators are released by white blood cells and determine if we can inhibit this effect with existing and new drugs. We would also like to see the effect of these drugs on the life-span and function of white blood cells. We will compare the behaviour and characteristics of white cells with those from healthy smokers and healthy non-smokers to find out if there is anything different about cells from COPD patients.

Clinical Trial Description

The aim of this study is to investigate the mechanisms that regulate the survival of blood leukocytes as well as the synthesis and release of inflammatory mediators from cells from normal individuals and subjects with COPD. The hypothesis is that in COPD the life-span of leukocytes, such as the neutrophil, is enhanced and this may contribute to inflammation, a prominent characteristic of this disease, by secreting and releasing inflammatory mediators. We also suggest that differences may exist in the sensitivity of the various leukocytes to different therapies.

Leukocytes will be purified from the peripheral venous blood of patients with COPD as well as healthy individuals. We will then investigate the effects of novel and existing therapeutic agents on leukocyte survival and inflammatory mediator synthesis and release. We will also examine the regulation and release of enzymes known to damage lung tissue. Further studies will be carried out to elucidate the signal transduction pathways that lead to the activation, altered longevity and function of leukocytes. In other experiments ribonucleic acids or RNA may be extracted form leukocytes to investigate which genes are involved. The primary objective is to identify the mechanisms that enhance leukocyte longevity and inflammatory mediator and/or enzyme synthesis and release with a view to identifying novel targets for drug therapy. ;

Related Conditions & MeSH terms

• Chronic Obstructive Airway Disease
• Healthy Volunteers
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

• NCT number: NCT00180765
• Study type: Observational
• Source: Imperial College London
• Status: Withdrawn
• Start date: October 2001
• Completion date: February 2008