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Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics)

Eiditor-in-Chief

ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Pharmacogenomics and Sepsis-Induced Renal Failure: Effects of β 2-Adrenoceptor Function on the Course of Sepsis

Author(s): Akio Nakamura and Yukishige Yanagawa

Volume 6 , Issue 2 , 2008

Page: [98 - 107] Pages: 10

DOI: 10.2174/1875692110806020098

Price: $58

Abstract

Endotoxemia caused by Gram-negative bacteria can result in sepsis and organ dysfunction, which includes kidney damage and renal failure. Genetic polymorphisms in cytokine-encoding genes contribute to individual variance in inflammatory responses and have been postulated as being associated with an increased risk for cytokine-mediated disorders, such as sepsis-induced acute renal failure. There is a growing body of evidence that the β2-adrenoceptor (β2-AR) system has an anti-inflammatory influence on the cytokine network during the course of immunological responses. Indeed, activation of β2-ARs can modulate the production of pro- and anti-inflammatory cytokines, such as TNF-β and interleukin( IL)-1, -6, -10, -12, in some tissues and organs. An altered expression or function of β2-ARs has been considered to be a pathogenetic factor in some inflammatory states; for example, allergy, heart failure and renal failure. Previously, we demonstrated that the application of adenoviral mediated β2-AR gene delivery to enhance renal β2-AR activity afforded the kidney protection against endotoxin-induced acute renal failure. These observations would suggest the possibility that the level of β2-AR activity might be associated with β2-AR polymorphisms which may pre-determine the increased risk of organ dysfunction following severe sepsis. At present it seems that β2-AR polymorphisms do not play a role as sepsiscausing genes; however, they might be risk factors, might modify sepsis, and/or might influence the progression of sepsis. Thus, genomic information on β2-AR polymorphisms has a potential use to identify groups of patients with a raised risk of developing severe sepsis and multiple organ dysfunctions.


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