Abstract
Arginine is a semiessential amino acid in healthy adult human, but is essential for preterm, newborn or critically ill patients. Arginine can be supplied from our diet or de novo synthesis from citrulline. In conditions of sepsis or endotoxemia, arginine may be deficient and be accompanied with altered immune response. L-arginine supplementation can ameliorate dysregulated immune condition and improve prognosis. Many studies had tried L-arginine or L-citrulline supplementation to examine the effect on immune response in the adult population. Few had studied on the young children. In this study, we determined the effect of L-arginine and L-citrulline supplementation on the immune response of infantile rats. Male infantile rats received normal saline, L-arginine (200 mg/kg/day) or L-citrulline (200 mg/kg/day) intraperitoneally over postnatal day 8 to day 14. The infantile rats were then sacrificed. The blood was analyzed while the spleen was indicated for immune analysis after stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS). We found L-arginine supplementation enhanced Th1 immune response by increasing IFN-γ production. Both the L-arginine and L-citrulline therapy can modulate regulatory T-cell (Treg) immune effects by increasing the IL-10 level. Only the L-citrulline group showed a TGF-β1 increase. Both L-arginine and L-citrulline therapy were also noted to decrease SMAD7 expression and enhance SIRT-1 abundance. However, FOXP3 expression was only modulated by L-citrulline treatment. We then concluded that L-arginine and L-citrulline supplementation can modulate the regulatory T-cells function differently for infantile rats.
Highlights
Arginine is a semi-essential amino acid in human depending on the developmental stage or health status of the individual
After postnatal administration of L-arginine, L-citrulline, or normal saline, the body weight at postnatal day 15 were similar among the three groups (Table 1)
Arginine is an amino acid that plays a key role in the immune system
Summary
Arginine is a semi-essential amino acid in human depending on the developmental stage or health status of the individual. Arginine deficiency is related to decreased arginine uptake and impaired arginine de novo synthesis from citrulline, in combination with an enhanced arginine catabolism by the up-regulation of arginase and the nitric oxide synthase (NOs) in the immune response [6]. NOs is stimulated by Th1 cytokines such as interferon-gamma (IFN)-γ and interleukin (IL)-1 which play important roles in intracellular defense against microorganisms while arginase is activated by Th2 related cytokines such as IL4, IL-5, and IL-13 which are responsible for allergic reactions [7, 8]. The role of regulatory T cells (Treg) is to suppress over-activated effector T cells and play a key role in the regulation of Th1/Th2 immune responses [9,10,11]. Treg secrets regulatory cytokines such as transforming growth factor (TGF)-β and IL-10 [12]
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