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 )

Bronchial mucosal expression of
pro-eosinophilic cytokines
in atopic and nonatopic asthma
Marc Humbert
Service de Pneumologie et Réanimation Respiratoire
Institut Paris Sud sur les Cytokines Hôpital Antoine Béclère
157, rue de la Porte de Trivaux, 92 140 Clamart, France
Tel: (33) 1-45 37 47 76, Fax: (33) 1-46 30 38 24,
Email: marc.humbert (at) inserm.ipsc.u-psuc.fr

Irrespective of its atopic status, asthma is associated with eosinophil-rich inflammation of the bronchial mucosa, even in mild disease. A large number of mediators produced by different cell types including activated T-lymphocytes could play a major part in regulating the successive steps leading to a characteristic eosinophil-rich airways inflammation.

We will present some recent data on pro-eosinophilic cytokine expression in the submucosa of asthmatic individuals.

Using semiquantitative polymerase reaction, in situ hybridization and immunocytochemistry we have shown elevated expression of IL-4 and IL-5 mRNA and protein product in bronchial biopsies collected in atopic and non atopic asthmatics. In these patients the numbers of IL-5 mRNA molecules relative to b-actin molecules correlated with markers of asthma severity. Conversely, the numbers of IL-4 mRNA molecules relative to b-actin molecules correlated with total serum IgE, suggesting that IL-5 was a better marker of asthma and IL-4 a better marker of atopy. More than 70% of IL-4 and IL-5 mRNA+ cells were CD4+ T lymphocytes, supporting the concept that T helper cells play a major role in orchestrating the asthmatic inflammation.

Similarly mRNA expression of IL-13, IL-3, GM-CSF, RANTES and MCP-3 was elevated in bronchial biopsies of asthmatic individuals. Although expression of these cytokine did not correlate with markers of asthma severity, combined expression in vivo may play a major role in promoting chronic eosinophilic inflammation. One of the most important perspective in this area is the detailed analysis of CC chemokine eotaxin and its receptor CCR3 (shared with RANTES and MCP-3).

Targeting pro-eosinophilic cytokines in vivo may provide new therapeutic tools in asthma.