Citrulline

A potential immunomodulator in sepsis

Theodor Asgeirsson, Sen Zhang, Robert Nunoo, Christopher Mascarenas, Nadav Dujovny, Martin Luchtefeld, Greg S. Cavey, Anthony Senagore

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Sepsis leads to a complex systemic response of cytokines (both pro- and anti-inflammatory) and more recently recognized adipokine mediators. Endothelial nitric oxide (NO) may be a key component in regulating this response, but the pharmacologic manipulation of endothelial NO via L-arginine supplementation or inhibitors has provided inconsistent clinical data related to outcomes. These failures are related to the metabolism of L-arginine in the liver, toxicity of L-arginine, and asymmetric dimethylarginine inhibition, all of which may explain the "arginine paradox." L-citrulline (CIT) offers a potentially valuable means of supplementing arginine and therefore impacting favorably NO availability. The goal of this study was to determine whether CIT supplementation altered the systemic response of mediators and cytokines in a rat model of sepsis with varying degrees of severity. Methods: Sepsis was induced with 2 models of cecal ligation and puncture (CLP) of varying severity in Wistar rats. CIT supplementation was provided to half the animals as 8% CIT-supplemented feed for 3 weeks. Baseline mediator levels were assessed in the Wistar rats followed by comparison of the following groups at days 0, 1, and 3: sham-operated; CLP 8-mm (localized); and CLP 12-mm (extensive). The following analyses were performed in the groups: interleukin-6 (IL-6), IL-8, IL-10, resistin, and adiponectin levels (enzyme-linked immunosorbent assay performed in duplicate). L-arginine and CIT were measured with high-performance liquid chromatography combined with mass spectrometry. Results: Ninety-eight Wistar rats were evaluated, and survival was similar in both sepsis models with and without CIT. Serum IL-6 levels were lower in the CIT/CLP 8-mm group compared to the standard rat chow (STD)/CLP 8-mm group (41 vs 117 pg/mL; P =.011) on postoperative day 3. Serum IL-8 and IL-10 responses were similar across all groups. Serum resistin levels were lower in the CIT/CLP 12-mm group compared to the STD/CLP 12-mm group in the more severe sepsis model on day 3 (19 vs 38 ng/mL; P

Original languageEnglish (US)
Pages (from-to)744-751
Number of pages8
JournalSurgery
Volume150
Issue number4
DOIs
StatePublished - Oct 2011
Externally publishedYes

Fingerprint

Citrulline
Immunologic Factors
Punctures
Sepsis
Ligation
Arginine
Resistin
Wistar Rats
Nitric Oxide
Sexually Transmitted Diseases
Interleukin-8
Interleukin-10
Interleukin-6
Serum
Cytokines
Adipokines
Adiponectin
Mass Spectrometry
Anti-Inflammatory Agents
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Surgery

Cite this

Asgeirsson, T., Zhang, S., Nunoo, R., Mascarenas, C., Dujovny, N., Luchtefeld, M., ... Senagore, A. (2011). Citrulline: A potential immunomodulator in sepsis. Surgery, 150(4), 744-751. https://doi.org/10.1016/j.surg.2011.08.024

Citrulline : A potential immunomodulator in sepsis. / Asgeirsson, Theodor; Zhang, Sen; Nunoo, Robert; Mascarenas, Christopher; Dujovny, Nadav; Luchtefeld, Martin; Cavey, Greg S.; Senagore, Anthony.

In: Surgery, Vol. 150, No. 4, 10.2011, p. 744-751.

Research output: Contribution to journalArticle

Asgeirsson, T, Zhang, S, Nunoo, R, Mascarenas, C, Dujovny, N, Luchtefeld, M, Cavey, GS & Senagore, A 2011, 'Citrulline: A potential immunomodulator in sepsis', Surgery, vol. 150, no. 4, pp. 744-751. https://doi.org/10.1016/j.surg.2011.08.024
Asgeirsson T, Zhang S, Nunoo R, Mascarenas C, Dujovny N, Luchtefeld M et al. Citrulline: A potential immunomodulator in sepsis. Surgery. 2011 Oct;150(4):744-751. https://doi.org/10.1016/j.surg.2011.08.024
Asgeirsson, Theodor ; Zhang, Sen ; Nunoo, Robert ; Mascarenas, Christopher ; Dujovny, Nadav ; Luchtefeld, Martin ; Cavey, Greg S. ; Senagore, Anthony. / Citrulline : A potential immunomodulator in sepsis. In: Surgery. 2011 ; Vol. 150, No. 4. pp. 744-751.
@article{9898d501bc354049b17b4703ba51d935,
title = "Citrulline: A potential immunomodulator in sepsis",
abstract = "Background: Sepsis leads to a complex systemic response of cytokines (both pro- and anti-inflammatory) and more recently recognized adipokine mediators. Endothelial nitric oxide (NO) may be a key component in regulating this response, but the pharmacologic manipulation of endothelial NO via L-arginine supplementation or inhibitors has provided inconsistent clinical data related to outcomes. These failures are related to the metabolism of L-arginine in the liver, toxicity of L-arginine, and asymmetric dimethylarginine inhibition, all of which may explain the {"}arginine paradox.{"} L-citrulline (CIT) offers a potentially valuable means of supplementing arginine and therefore impacting favorably NO availability. The goal of this study was to determine whether CIT supplementation altered the systemic response of mediators and cytokines in a rat model of sepsis with varying degrees of severity. Methods: Sepsis was induced with 2 models of cecal ligation and puncture (CLP) of varying severity in Wistar rats. CIT supplementation was provided to half the animals as 8{\%} CIT-supplemented feed for 3 weeks. Baseline mediator levels were assessed in the Wistar rats followed by comparison of the following groups at days 0, 1, and 3: sham-operated; CLP 8-mm (localized); and CLP 12-mm (extensive). The following analyses were performed in the groups: interleukin-6 (IL-6), IL-8, IL-10, resistin, and adiponectin levels (enzyme-linked immunosorbent assay performed in duplicate). L-arginine and CIT were measured with high-performance liquid chromatography combined with mass spectrometry. Results: Ninety-eight Wistar rats were evaluated, and survival was similar in both sepsis models with and without CIT. Serum IL-6 levels were lower in the CIT/CLP 8-mm group compared to the standard rat chow (STD)/CLP 8-mm group (41 vs 117 pg/mL; P =.011) on postoperative day 3. Serum IL-8 and IL-10 responses were similar across all groups. Serum resistin levels were lower in the CIT/CLP 12-mm group compared to the STD/CLP 12-mm group in the more severe sepsis model on day 3 (19 vs 38 ng/mL; P",
author = "Theodor Asgeirsson and Sen Zhang and Robert Nunoo and Christopher Mascarenas and Nadav Dujovny and Martin Luchtefeld and Cavey, {Greg S.} and Anthony Senagore",
year = "2011",
month = "10",
doi = "10.1016/j.surg.2011.08.024",
language = "English (US)",
volume = "150",
pages = "744--751",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - Citrulline

T2 - A potential immunomodulator in sepsis

AU - Asgeirsson, Theodor

AU - Zhang, Sen

AU - Nunoo, Robert

AU - Mascarenas, Christopher

AU - Dujovny, Nadav

AU - Luchtefeld, Martin

AU - Cavey, Greg S.

AU - Senagore, Anthony

PY - 2011/10

Y1 - 2011/10

N2 - Background: Sepsis leads to a complex systemic response of cytokines (both pro- and anti-inflammatory) and more recently recognized adipokine mediators. Endothelial nitric oxide (NO) may be a key component in regulating this response, but the pharmacologic manipulation of endothelial NO via L-arginine supplementation or inhibitors has provided inconsistent clinical data related to outcomes. These failures are related to the metabolism of L-arginine in the liver, toxicity of L-arginine, and asymmetric dimethylarginine inhibition, all of which may explain the "arginine paradox." L-citrulline (CIT) offers a potentially valuable means of supplementing arginine and therefore impacting favorably NO availability. The goal of this study was to determine whether CIT supplementation altered the systemic response of mediators and cytokines in a rat model of sepsis with varying degrees of severity. Methods: Sepsis was induced with 2 models of cecal ligation and puncture (CLP) of varying severity in Wistar rats. CIT supplementation was provided to half the animals as 8% CIT-supplemented feed for 3 weeks. Baseline mediator levels were assessed in the Wistar rats followed by comparison of the following groups at days 0, 1, and 3: sham-operated; CLP 8-mm (localized); and CLP 12-mm (extensive). The following analyses were performed in the groups: interleukin-6 (IL-6), IL-8, IL-10, resistin, and adiponectin levels (enzyme-linked immunosorbent assay performed in duplicate). L-arginine and CIT were measured with high-performance liquid chromatography combined with mass spectrometry. Results: Ninety-eight Wistar rats were evaluated, and survival was similar in both sepsis models with and without CIT. Serum IL-6 levels were lower in the CIT/CLP 8-mm group compared to the standard rat chow (STD)/CLP 8-mm group (41 vs 117 pg/mL; P =.011) on postoperative day 3. Serum IL-8 and IL-10 responses were similar across all groups. Serum resistin levels were lower in the CIT/CLP 12-mm group compared to the STD/CLP 12-mm group in the more severe sepsis model on day 3 (19 vs 38 ng/mL; P

AB - Background: Sepsis leads to a complex systemic response of cytokines (both pro- and anti-inflammatory) and more recently recognized adipokine mediators. Endothelial nitric oxide (NO) may be a key component in regulating this response, but the pharmacologic manipulation of endothelial NO via L-arginine supplementation or inhibitors has provided inconsistent clinical data related to outcomes. These failures are related to the metabolism of L-arginine in the liver, toxicity of L-arginine, and asymmetric dimethylarginine inhibition, all of which may explain the "arginine paradox." L-citrulline (CIT) offers a potentially valuable means of supplementing arginine and therefore impacting favorably NO availability. The goal of this study was to determine whether CIT supplementation altered the systemic response of mediators and cytokines in a rat model of sepsis with varying degrees of severity. Methods: Sepsis was induced with 2 models of cecal ligation and puncture (CLP) of varying severity in Wistar rats. CIT supplementation was provided to half the animals as 8% CIT-supplemented feed for 3 weeks. Baseline mediator levels were assessed in the Wistar rats followed by comparison of the following groups at days 0, 1, and 3: sham-operated; CLP 8-mm (localized); and CLP 12-mm (extensive). The following analyses were performed in the groups: interleukin-6 (IL-6), IL-8, IL-10, resistin, and adiponectin levels (enzyme-linked immunosorbent assay performed in duplicate). L-arginine and CIT were measured with high-performance liquid chromatography combined with mass spectrometry. Results: Ninety-eight Wistar rats were evaluated, and survival was similar in both sepsis models with and without CIT. Serum IL-6 levels were lower in the CIT/CLP 8-mm group compared to the standard rat chow (STD)/CLP 8-mm group (41 vs 117 pg/mL; P =.011) on postoperative day 3. Serum IL-8 and IL-10 responses were similar across all groups. Serum resistin levels were lower in the CIT/CLP 12-mm group compared to the STD/CLP 12-mm group in the more severe sepsis model on day 3 (19 vs 38 ng/mL; P

UR - http://www.scopus.com/inward/record.url?scp=80054091482&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054091482&partnerID=8YFLogxK

U2 - 10.1016/j.surg.2011.08.024

DO - 10.1016/j.surg.2011.08.024

M3 - Article

VL - 150

SP - 744

EP - 751

JO - Surgery

JF - Surgery

SN - 0039-6060

IS - 4

ER -