( Disruption of a single gene Nrf2 play...)Researches discover gene critical for protection against septic-shock-induced death

The researchers found that the absence of Nrf2 caused a dramatic increase in mortality due to septic shock in mice. The study's findings, which will be published in the April 2006 issue of the Journal of Clinical Investigation, may hold potential for the treatment of life-threatening sepsis.

Sepsis is a complex disease characterized by an increased inflammatory response in the body's attempt to combat an infection from microorganisms such as bacteria, fungi or viruses. A weak host inflammatory response can lead to greater infection, whereas an excessive inflammatory response may lead to tissue damage, myocardial injury, acute respiratory failure, multiple organ failure or death. Controlling inflammation is thus a central focus of treating sepsis. Researchers have been hunting for novel host genes that regulate inflammation as potential targets for the next generation of sepsis therapies. The incidence of sepsis in the United States ranges from 400,000 to 750,000 cases per year. Mortality due to sepsis is around 30 percent and increases with age from 10 percent in children to 40 percent in the elderly. Mortality is 50 percent or greater in patients with the more severe syndrome, septic shock.

Suspecting that a dysregulation in the body's inflammatory response exacerbates sepsis, the research team began looking into the genetic factors that might contribute to this syndrome. In 2002, Biswal and his colleagues discovered that Nrf2 acts as a primary regulator of most of the cellular antioxidant pathways and detoxifying enzymes that protect the body from a wide variety of environmental toxicants. In subsequent studies, they discovered that Nrf2 is a pleiotropic protein thatregulates a broad spectr
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Source:Johns Hopkins University Bloomberg School of Public Health