Thèse soutenue

Rôle des phospholipases dans les interactions bactéries -cellules hôtes : implications dans la mucoviscidose

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Auteur / Autrice : Anne Dubouix
Direction : Jean-Pierre SallesNicole Marty
Type : Thèse de doctorat
Discipline(s) : Physiopathologie cellulaire, moléculaire, et intégrée. Microbiologie
Date : Soutenance en 2004
Etablissement(s) : Toulouse 3



Heightened and sustained neutrophilic airway inflammation is central to the pathogenesis of CF lung disease. Studies evaluating corticosteroids and ibuprofen have demonstrated potential benefits associated with antiinflammatory therapy. The challenge lies in finding drugs that combine effective antiinflammatory activity in the CF lung with an acceptable risk for adverse effects. Drugs targeting single cytokines or receptors might prove less effective due to the redundancies of inflammatory processes involved. Drugs affecting multiple molecules or key inflammatory pathway intermediates could be more effective, but their use will need to be weighed against the risk of impairing innate immunity. Indirect approaches to manage inflammation, such as neutralizing cytotoxic substances in the lung, could be used in combination with other approaches. Development of an orally active, small-molecule antiproteinase drug would be highly desirable in this regard. Rescue/correction of the Cftr defect is a longterm goal with the potential to address multiple facets of CF pathology, including inflammation. Combining one or more of these strategies with the existing treatments of pulmonary toilet and antibiotics may lead to improved clinical outcome.