Critical Care Medicine

Adult Critical Care

Citrulline: A potential immunomodulator in sepsis

Asgeirsson T, Zhang S, Nunoo R, et al (Spectrum Health Res, Grand Rapids, MI; Guangxi Med Univ, Nanning Guangxi, China; et al) Surgery 150:744-751, 2011^§

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.

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