Biology Reference
In-Depth Information
(Rietschel and Westphal, 1999). LPS released in a human host due to
bacterial growth or bacterial lysis interacts with a pattern-recognition
receptor complex present in many host cells including monocytes and
macrophages. This recognition event activates these cells to release
several pro-inflammatory cytokines, members of a large class of small
intercellular signaling molecules consisting of more than 160
polypeptides that orchestrate immune responses to invading pathogens
by allowing cells to communicate with one another. Among these
cytokines are tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1),
and interleukin-6 (IL-6). The cytokines then activate other phagocytic
cells and up-regulate the innate immune system in an attempt to clear the
invading microbe. This systemic inflammatory response to LPS leads to
sepsis. Sepsis is characterized by fever, mental confusion, diarrhea, and
hypotension. Severe sepsis, commonly referred to as
septic shock
syndrome
, is a very dangerous disease that can lead to organ damage and
even failure, and eventually death. An LPS concentration of less than
1 ng/mL is sufficient to cause the symptoms of sepsis, but more than
100 ng/mL is required to produce septic shock (Parrillo, 1993). After
septic shock onset, patients also can succumb to secondary infections
caused by opportunistic pathogens. That is, following the initial period of
hyperimmune response, several anti-inflammatory cytokines are released
to maintain homeostasis and as a result patients may become temporarily
immunodepressed and susceptible to other pathogens.
6.1.1.3
Impact on human health
Despite great efforts, sepsis continues to be a severe health problem with
mortality rates ranging between 20-40% overall, and 40-60% for septic
shock cases (Friedman
et al.
, 1998, Wheeler and Bernard, 1999).
Although the mortality rate has been decreasing over the last few
decades, it is still the tenth leading cause of death in the United States.
There were 660,000 cases (240 per 100,000 population) of sepsis
reported in 2000 according to a joint study by the Center for Disease
Control and Prevention and Emory University School of Medicine
(Martin
et al.
, 2003). It has been an especially difficult problem in men
(more common than in women by a factor of 1.28) and nonwhites (mean
