Citrulline: a potential immunomodulator in sepsis

Area of Science:

• Biochemistry
• Immunology
• Sepsis Research

Background:

• Sepsis involves complex cytokine and adipokine responses.
• Endothelial nitric oxide (NO) plays a regulatory role, but L-arginine supplementation has yielded inconsistent results due to factors like liver metabolism and inhibition.
• L-citrulline (CIT) offers a promising alternative for arginine and NO supplementation.

Purpose of the Study:

• To investigate if CIT supplementation alters mediator and cytokine responses in a rat model of sepsis.
• To assess the impact of CIT on systemic inflammation in varying degrees of sepsis severity.

Main Methods:

• Sepsis was induced using cecal ligation and puncture (CLP) in Wistar rats.
• Animals received either standard chow or 8% CIT-supplemented feed for three weeks.
• Serum levels of IL-6, IL-8, IL-10, resistin, adiponectin, L-arginine, and CIT were measured using ELISA and HPLC-MS.

Main Results:

• CIT supplementation did not affect survival rates in sepsis models.
• Serum IL-6 levels were significantly lower in the CIT group for localized sepsis (CLP 8-mm) on day 3.
• Serum resistin levels were significantly lower in the CIT group for extensive sepsis (CLP 12-mm) on day 3.
• L-arginine levels were higher in CIT-supplemented rats prior to sepsis induction.

Conclusions:

• L-citrulline (CIT) may reduce pro-inflammatory mediators (IL-6, resistin) in sepsis.
• CIT supplementation appears to preserve anti-inflammatory mediator secretion (IL-10, adiponectin).
• CIT offers a potential safe immunomodulatory strategy in sepsis.