Sepsis,
septic shock, and multiple organ dysfunction are heterogeneous and sophisticated clinical syndromes which result from the interplay of mediators of cellular function and
inflammation. Secondary mediators such as
lipids (
prostaglandin,
thromboxane,
platelet-activating factor),
peptides (
bradykinin,
vasoactive intestinal peptide),
amines (
histamine,
serotonin) and complements are key mediators which lead to the state of
shock in human
sepsis.
Endotoxin may also cause
multiple organ dysfunction syndrome (
MODS). New antiendotoxin treatment and the strategy for
sepsis including
endotoxemia are reviewed.
Monoclonal antibodies directed at core
epitopes and
lipid A (E5, HA1-A) could not reproduce the beneficial effects.
Bactericidal/permeability increasing protein (BPI)).
Endotoxin neutralizing
protein (ENP)) and
E5531 may have potential in the treatment of
sepsis. Another treatment using extracorporeal
endotoxin removal is reported.
Polymyxin B immobilized fiber (PMX), commercialized as Toraymyxin, is now widely used in Japan for
severe sepsis and septic
MODS. PMX treatment improves the symptoms related to the septic state, a hemodynamic disorders, and
cytokine levels including
tumor mecrosis factor,
interleukin (IL)-6, and IL-10, with a decrease in
endotoxin levels. Phase II, III, and IV clinical trials with extracorporeal
endotoxin removal by PMX revealed that
endotoxin removal is helpful in the treatment of septic patients.