Current knowledge about the pathophysiology of
septic shock is reviewed, and biotechnology-based
therapies under development are discussed. Patients with
septic shock begin their
clinical course with
leukocytosis,
fever,
tachycardia,
tachypnea, and organ hypoperfusion;
shock ensues as immunologic and vasoactive mediators produce
hypotension. There are many metabolic and cardiovascular responses, and single- or
multiple-organ failure is common. Patients may experience
adult respiratory distress syndrome. A multitude of endogenous and exogenous factors have been linked to the pathophysiology of
sepsis and
septic shock, including (1)
endotoxin from gram-negative bacteria, (2)
peptidoglycan and
exotoxins from gram-negative bacteria, (3)
endotoxin-binding proteins and receptors, (4) bactericidal
proteases, (5)
exotoxins from gram-positive bacteria, (6)
acute-phase proteins and
proteases, (7)
cytokines, (8)
arachidonic acid metabolites, (9)
complement, (10)
beta-endorphin, (11)
histamine, (12) stimulation of intrinsic and extrinsic coagulation pathways and
proteases, and (13) endothelium-derived factors and adhesion molecules. Molecular entities and strategies under development to combat
septic shock include
monoclonal antibodies to
endotoxin, active immunization with
lipid-A analogues,
bactericidal permeability-increasing protein,
interleukin inhibitors, and inhibitors of
tumor necrosis factor-alpha. Successful treatment of
septic shock will probably require a combination of agents, including antimicrobials. An ideal goal for biotechnology in the area of
septic shock is to prevent invading pathogens from overstimulating the host's immune system and to systematically eliminate those pathogens. Biotechnology is opening new avenues to the treatment of
septic shock.