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Alterations in Leukocyte Function following Surgical Trauma: Differentiation of Distinct Reaction Types and Association with Tumor Necrosis Factor Gene Polymorphisms

Alterations in Leukocyte Function following Surgical Trauma: Differentiation of Distinct Reaction... Endotoxin-stimulated blood cytokine responses have been widely used to describe compromised host defense mechanisms after trauma. We investigated whether blood cytokine production after endotoxin stimulation is able to define distinct trauma-induced alteration patterns and whether alteration patterns are associated with tumor necrosis factor (TNF) gene polymorphisms. In 48 patients undergoing joint replacement, the levels of TNF alpha (TNF- ), interleukin 6 (IL-6), and IL-8 production in blood after endotoxin stimulation were measured preoperatively on the day of surgery and 24 h thereafter. Patients were genotyped for the TNF- position –308 G/A polymorphism and the TNF-ß NcoI polymorphism. Postoperative alterations, i.e., increases or decreases of cytokine levels (TNF- versus IL-6, P = 0.013; TNF- versus IL-8, P = 0.001; IL-6 versus IL-8, P = 0.007), and relative postoperative changes, i.e., percentages of preoperative cytokine levels (TNF- versus IL-6, r s = 0.491, P < 0.001; TNF- versus IL-8, r s = 0.591, P < 0.001; IL-6 versus IL-8, r s = 0.474, P < 0.001 where r s is the Spearman rank correlation coefficient), had significant positive correlations among the cytokines. Overall enhanced postoperative alteration patterns were found in 10 patients, attenuated patterns were found in 18 patients, and mixed patterns were found in 20 patients. Preoperative cytokine production levels differed significantly between these groups (those of the overall enhanced pattern group were less than those of the mixed pattern group, which were less than those of the overall attenuated pattern group). TNF polymorphisms were not associated with overall alteration patterns, but the A*TNFB1 haplotype was associated with a postoperative increase in TNF- production ( P = 0.042). Whole-blood cytokine responses to endotoxin define the following preexisting patterns in leukocyte function: low baseline production and overall enhanced alteration patterns after trauma (type 1), intermediate baseline production and mixed alteration patterns (type 2), and high baseline production and overall attenuated alteration patterns (type 3). TNF gene polymorphisms were associated with changes in TNF- production but do not explain the overall reaction patterns of cytokine production after trauma. The clinical correlate of these newly defined reaction types remains to be determined. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical and Vaccine Immunology American Society For Microbiology

Alterations in Leukocyte Function following Surgical Trauma: Differentiation of Distinct Reaction Types and Association with Tumor Necrosis Factor Gene Polymorphisms

Alterations in Leukocyte Function following Surgical Trauma: Differentiation of Distinct Reaction Types and Association with Tumor Necrosis Factor Gene Polymorphisms

Clinical and Vaccine Immunology , Volume 12 (2): 296 – Feb 1, 2005

Abstract

Endotoxin-stimulated blood cytokine responses have been widely used to describe compromised host defense mechanisms after trauma. We investigated whether blood cytokine production after endotoxin stimulation is able to define distinct trauma-induced alteration patterns and whether alteration patterns are associated with tumor necrosis factor (TNF) gene polymorphisms. In 48 patients undergoing joint replacement, the levels of TNF alpha (TNF- ), interleukin 6 (IL-6), and IL-8 production in blood after endotoxin stimulation were measured preoperatively on the day of surgery and 24 h thereafter. Patients were genotyped for the TNF- position –308 G/A polymorphism and the TNF-ß NcoI polymorphism. Postoperative alterations, i.e., increases or decreases of cytokine levels (TNF- versus IL-6, P = 0.013; TNF- versus IL-8, P = 0.001; IL-6 versus IL-8, P = 0.007), and relative postoperative changes, i.e., percentages of preoperative cytokine levels (TNF- versus IL-6, r s = 0.491, P < 0.001; TNF- versus IL-8, r s = 0.591, P < 0.001; IL-6 versus IL-8, r s = 0.474, P < 0.001 where r s is the Spearman rank correlation coefficient), had significant positive correlations among the cytokines. Overall enhanced postoperative alteration patterns were found in 10 patients, attenuated patterns were found in 18 patients, and mixed patterns were found in 20 patients. Preoperative cytokine production levels differed significantly between these groups (those of the overall enhanced pattern group were less than those of the mixed pattern group, which were less than those of the overall attenuated pattern group). TNF polymorphisms were not associated with overall alteration patterns, but the A*TNFB1 haplotype was associated with a postoperative increase in TNF- production ( P = 0.042). Whole-blood cytokine responses to endotoxin define the following preexisting patterns in leukocyte function: low baseline production and overall enhanced alteration patterns after trauma (type 1), intermediate baseline production and mixed alteration patterns (type 2), and high baseline production and overall attenuated alteration patterns (type 3). TNF gene polymorphisms were associated with changes in TNF- production but do not explain the overall reaction patterns of cytokine production after trauma. The clinical correlate of these newly defined reaction types remains to be determined.

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References (29)

Publisher
American Society For Microbiology
Copyright
Copyright © 2005 by the American Society For Microbiology.
ISSN
1556-6811
eISSN
1556-6811
DOI
10.1128/CDLI.12.2.296-303.2005
Publisher site
See Article on Publisher Site

Abstract

Endotoxin-stimulated blood cytokine responses have been widely used to describe compromised host defense mechanisms after trauma. We investigated whether blood cytokine production after endotoxin stimulation is able to define distinct trauma-induced alteration patterns and whether alteration patterns are associated with tumor necrosis factor (TNF) gene polymorphisms. In 48 patients undergoing joint replacement, the levels of TNF alpha (TNF- ), interleukin 6 (IL-6), and IL-8 production in blood after endotoxin stimulation were measured preoperatively on the day of surgery and 24 h thereafter. Patients were genotyped for the TNF- position –308 G/A polymorphism and the TNF-ß NcoI polymorphism. Postoperative alterations, i.e., increases or decreases of cytokine levels (TNF- versus IL-6, P = 0.013; TNF- versus IL-8, P = 0.001; IL-6 versus IL-8, P = 0.007), and relative postoperative changes, i.e., percentages of preoperative cytokine levels (TNF- versus IL-6, r s = 0.491, P < 0.001; TNF- versus IL-8, r s = 0.591, P < 0.001; IL-6 versus IL-8, r s = 0.474, P < 0.001 where r s is the Spearman rank correlation coefficient), had significant positive correlations among the cytokines. Overall enhanced postoperative alteration patterns were found in 10 patients, attenuated patterns were found in 18 patients, and mixed patterns were found in 20 patients. Preoperative cytokine production levels differed significantly between these groups (those of the overall enhanced pattern group were less than those of the mixed pattern group, which were less than those of the overall attenuated pattern group). TNF polymorphisms were not associated with overall alteration patterns, but the A*TNFB1 haplotype was associated with a postoperative increase in TNF- production ( P = 0.042). Whole-blood cytokine responses to endotoxin define the following preexisting patterns in leukocyte function: low baseline production and overall enhanced alteration patterns after trauma (type 1), intermediate baseline production and mixed alteration patterns (type 2), and high baseline production and overall attenuated alteration patterns (type 3). TNF gene polymorphisms were associated with changes in TNF- production but do not explain the overall reaction patterns of cytokine production after trauma. The clinical correlate of these newly defined reaction types remains to be determined.

Journal

Clinical and Vaccine ImmunologyAmerican Society For Microbiology

Published: Feb 1, 2005

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