Congress Sponsors Search Write About màj 23/07/98

ENFUMOSA (courriel: Chanez (at) montp.inserm.fr ) The European Network For Understanding Mechanisms of Severe Asthma BIOMED 2 Program - European Commission 4th quaterly meeting, with the support of INSERM and Merck Sharp & Dhome Laboratory February 13-14th 1998 in Montpellier- France (see programm, abstracts and experts comments ) Leukotrienes biosynthesis in severe asthma. Isabelle Vachier INSERM U454, Montpellier, France. Samedi 14 Février 1998 Présentateurs Modérateurs Experts 9h00-10h00 Marqueurs de l'inflamation P. Devillers (Lyon) I. Vachier (Montpellier) I. Pin (Grenoble) Discussion 10' 10' 10' 30' M. Fournier (Paris) B. Crestani (Paris) S.E. Dahlen (Stockholm, S) A.C. Roldaan (Davos, CH) K. Richter (Grossandorf, D) Introduction Bronchial asthma is now clearly defined as an inflammatory disorder of the bronchi. Patients with asthma have increased numbers of various types of inflammatory cells within the airways. These cells are activated and produce a variety of inflammatory mediators including leukotrienes. There is increasing evidence that leukotrienes play an important role in the pathophysiology of asthma. Asthma has been classified through different criteria of severity. There is a group of asthmatic patients who required oral and inhaled permanent therapy with steroids. This group of patients represent the most severe asthmatics and required a long term follow-up to better control their symptoms. The aim of our study was to compare the pattern of eicosanoid metabolites found in biological fluids and generated by isolated cells in this group of severe asthmatic patients to those found in untreated asthmatics.

Materials and Methods

A population of severe asthmatic patients with a follow-up for at least 1 year in our out-patient clinic was investigated and compared to a population of mild to moderate asthmatic patients without steroid treatment.

Blood cells, such as monocytes and neutrophils, and alveolar macrophages were isolated, purified and stimulated with Calcium-Ionophore (with and without additional metabolites) to study their ability to release leukotrienes and HETEs from both group of patients.

Biological fluids such as supernatant of induced sputum and urine were obtained from both groups. The level of leukotrienes and HETEs were measured .

Leukotrienes and HETEs produced by cells and found in the biological fluids were analysed using HPLC or ELISA kit extract.

Results

We found that stimulated blood monocytes obtained from severe asthmatic patients were able to produce smaller quantity of LTB4, and generated increase level of lipoxins and an unknown product (a possible anti-inflammatory mediator) when incubated with 15-HETE as compared to untreated asthmatics.

Moreover, stimulated blood neutrophils from these severe asthmatics released smaller amounts of LTB4 and its isomers, and also 5-, 15-diHETE when incubated with 15-HETE.

Stimulated alveolar macrophages produced very low quantities of LTB4 and 5-HETE.

However, the levels of LTB4 and LTE4 in supernatants of induced sputum, and, the level of LTE4 in urines were found to be significantly increased in severe asthmatic patients.

Conclusion

The results found in this study are quite surprising and controversal. Despite the steroid treatment, leukotrienes are found increase in the biological fluids. In contrast cells isolated from these severe steroid-dependent asthmatic patients have a reduce 5-lipoxygenase activity.

We need to perform further study to investigate the membrane integrety of the cells of these patients, to know if the measurement of leukotrienes production by the cells would be a suitable method to analyse the activation of the cells. If long term treatment with steroids affect the integrity of the plasma membrane, the method we used to investigate cells won't be suitable in such patients, and Calcium Ionophore stimulation dis not reflect the activation state of the cells.

In this case, the measurements of leukotrienes in biological fluids could be a better index of in vivo leukotriene production.

. Asmanet ENFUMOSA Congrès Conçue et réalisée par: Michel Godard (at) Top
Date de création: 5 Décembre 1997-Dernière mise à jour: 23/07/98
Le secret des correspondances transmises sur le réseau Internet n'est pas garanti.
Toute personne citée dispose d'un droit d'accès, de modification, de rectification et de suppression des données le concernant (art. 34 de la loi "Informatique et Libertés" n° 78-17 du 6 janvier 1978). Pour l'éxercer adressez-vous à Michel Godard (at)