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Article has an altmetric score of 3

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Referenced in 2 patents
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Research Article Free access | 10.1172/JCI116306

Tolerance to endotoxin-induced expression of the interleukin-1 beta gene in blood neutrophils of humans with the sepsis syndrome.

C E McCall, L M Grosso-Wilmoth, K LaRue, R N Guzman, and S L Cousart

Department of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157.

Find articles by McCall, C. in: JCI | PubMed | Google Scholar

Department of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157.

Find articles by Grosso-Wilmoth, L. in: JCI | PubMed | Google Scholar

Department of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157.

Find articles by LaRue, K. in: JCI | PubMed | Google Scholar

Department of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157.

Find articles by Guzman, R. in: JCI | PubMed | Google Scholar

Department of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157.

Find articles by Cousart, S. in: JCI | PubMed | Google Scholar

Published March 1, 1993 - More info

Published in Volume 91, Issue 3 on March 1, 1993
J Clin Invest. 1993;91(3):853–861. https://doi.org/10.1172/JCI116306.
© 1993 The American Society for Clinical Investigation
Published March 1, 1993 - Version history
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Abstract

The induction of genes of host cells stimulated by microbial products such as endotoxin and the tolerance of cells to endotoxin excitation play critical roles in the pathogenesis of microbial-induced acute disseminated inflammation with multiorgan failure (the sepsis syndrome). One gene that is induced in phagocytic cells by endotoxin and that appears to play an essential role in the pathogenesis of the sepsis syndrome is IL-1 beta. We report here that blood neutrophils (PMN) of patients with the sepsis syndrome (sepsis PMN) are consistently tolerant to endotoxin-induced expression of the IL-1 beta gene, as determined by decreased synthesis of the IL-1 beta protein and reductions in IL-1 beta mRNA. This down-regulation of the IL-1 beta gene in sepsis PMN occurs concomitant with an upregulation in the constitutive expression of the type 2 IL-1 receptor (IL-1R2). These phenotypic changes do not persist in PMN of patients recovering from the sepsis syndrome. Tolerance has stimulus and response specificity since sepsis PMN tolerant to endotoxin can respond normally to Staphylococcus aureus stimulation of IL-1 beta production and they normally secrete elastase. Uninfected patients with severe trauma or shock from causes are not tolerant to endotoxin and tolerance is not limited to patients infected with Gram-negative bacteria. The mechanism responsible for tolerance involves pretranslational events and is not due to loss of the CD14 surface protein, a receptor required for endotoxin induction of IL-1 beta in PMN. The physiological significance of the tolerance to endotoxin and increased expression of IL-1R2 on sepsis PMN is unknown, but may represent an attempt by the host to protect itself from the deleterious effects of disseminated inflammation.

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Referenced in 2 patents
31 readers on Mendeley
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