Chapter category:

Lipid A-Mediated Tolerance and Cancer Therapy

This chapter appears in the following book:

Lipid A in Cancer Therapy

Edited by: Jean-François Jeannin
ISBN: TBA
» Get more information about this book at landesbioscience.com «

Chapter authors:
Cheryl E. Rockwell, David. C. Morrison and Nilofer Qureshi

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The occurrence of tolerance or host unresponsiveness in animals and humans administered multiple doses of microbe or microbial products has long been recognized by scientists and physicians with published reports appearing in professional journals dating back to the 19th century.1 Many of the very early observations focused largely upon the establishment of pyrogen tolerance in which animals treated with a microbe or a microbial product exhibited a refractory state for the development of fever, or a markedly diminished fever response, upon subsequent treatments with the same or a related microbe or product. Following the identification and purification of lipopolysaccharide (LPS) in the 20th century, it was determined that the microbial product, LPS itself, can be highly tolerogenic.2 In this respect, many of the pleiotropic effects of LPS, including fever, induction of cytokine production and even mortality are absent or markedly diminished upon repeated administration of LPS. From these observations, it has been postulated that tolerance serves to protect the host from the detrimental consequences of the robust and extensive inflammatory responses that follow exposure to LPS. Tolerance cannot, however, be characterized as a global downregulation of responsiveness as some LPS-responsive characteristics remain unchanged or in some cases can actually be upregulated in experimental models of tolerance.

Cheryl E. Rockwell

David. C. Morrison

Nilofer Qureshi
Department of Basic Medical Science, School of Medicine, Shock/Trauma Research Center, University of Missouri, Kansas City, Missouri U.S.A.

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Chapter category:

Lipid A-Mediated Tolerance and Cancer Therapy

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