The role of cytokine overproduction in pathogenesis can be illustrated by bacterial septic shock. This condition may develop a few hours after infection by certain gram-negative bacteria, including E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter aerogenes, and Neisseria meningitidis. The symptoms of bacterial septic shock, which is often fatal, include a drop in blood pressure, fever, diarrhea, and widespread blood clotting in various organs. This condition afflicts about 500,000 Americans annually and causes more than 70,000 deaths. The annual cost for treating bacterial septic shock is estimated to be in excess of $5 billion.
Bacterial septic shock apparently develops because bacterial cell-wall endotoxins stimulate macrophages to overproduce IL-1 and TNF-a to levels that cause septic shock. In one study, for example, higher levels of TNF-a were found in patients who died of meningitis than in those who recovered. Furthermore, a condition resembling bacterial septic shock can be produced by injecting mice with recombinant TNF-a in the absence of gram-negative bacterial infection. Several studies offer some hope that neutralization of TNF-a or IL-1 activity with monoclonal antibodies or antagonists may prevent this fatal shock from developing in these bacterial infections. In one study, monoclonal antibody to TNF-a protected animals from endotoxin-induced shock. Another study has shown that injection of a recombinant IL-1 receptor antagonist (IL-1Ra), which prevents binding of IL-1 to the IL-1 receptor, resulted in a three-fold reduction in mortality. It is hoped that these experimental results will lead to clinically useful products for the treatment of bacterial septic shock in humans.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.