Role of flagellin in the pathogenesis of shock and acute respiratory distress syndrome: Therapeutic opportunities

Objective: To provide an overview of the role of flagellin as an immunostimulatory and proinflammatory factor. Design: A systematic overview of the literature on this subject. Setting: An office equipped with a computer and Internet access to PubMed. Subjects: MEDLINE citations between 1960 and 2002. Main Results: Flagellin, a protein of 40-60 kD, is the principal constituent of the flagellum, a prominent surface structure found in motile bacteria. Recent work reveals that monomeric flagellin, a protein component of flagellated bacteria, can act as a soluble immunostimulatory and proinflammatory factor, activating the immune/inflammatory axis via the toll-like receptor 5-nuclear factor-κB axis. Monocytes, macrophages, and intestinal and pulmonary epithelial cells respond to monomeric flagellin at low concentrations. Monomeric flagellin can induce prominent local and systemic immune/inflammatory responses in vitro and in vivo. Conclusions: Recognition of the flagellin-toll-like receptor 5 pathway offers novel opportunities for the experimental therapy of various forms of shock, sepsis, and acute respiratory distress syndrome.