The knowledge that agmatine
is found in the human body has existed for several years; however, its role in sepsis
has not yet been studied. In the present study, we investigate the role of agmatine
in the progression and treatment of sepsis
Medical centers/University-based research laboratory.
Elective ICU patients with severe sepsis
and healthy volunteers; C57BL/6 mice weighing 18–22 g.
level and its associations with inflammatory markers were assessed in patients with sepsis
was administered intraperitoneally to mice before a lipopolysaccharide challenge. Human peripheral blood mononuclear cells and murine macrophages were pretreated with agmatine
followed by lipopolysaccharide stimulation.
Measurements and Main Results:
levels were significantly decreased in patients with sepsis
and lipopolysaccharide-induced mice, and correlated with Acute Physiology and Chronic Health Evaluation II score, procalcitonin, tumor necrosis factor-α, and interleukin-6 levels. In a therapeutic experiment, exogenous agmatine
attenuated the cytokine production of peripheral blood mononuclear cells from patients with sepsis
and healthy controls. Agmatine
also exerted a significant beneficial effect in the inflammatory response and organ damage and reduced the death rate in lipopolysaccharide-induced mice. 2 receptor">Imidazoline I2 receptor
agonist 2-benzofuran-2-yl blocked the pharmacological action of agmatine
; whereas, other imidazoline receptor ligands did not. Furthermore, agmatine
significantly impaired the inflammatory response by inactivating nuclear factor-κB
, but not protein 38 mitogen-activated protein kinase, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and inducible nitric oxide synthase
signaling in macrophages. Activation of 2 receptor">imidazoline I2 receptor
or knockdown of ribosomal S6 kinase 2 counteracted the effects of agmatine
on phosphorylation and degradation of inhibitor of nuclear factor-κBα.
metabolism correlated with the progression of sepsis
. Supplemental exogenous agmatine
could ameliorate the lipopolysaccharide-induced systemic inflammatory responses and multiple organ injuries through the 2 receptor">imidazoline I2 receptor
-ribosomal S6 kinase 2-nuclear factor-κB
could be used as both a clinical biomarker and a promising pharmaconutrient in patients with severe sepsis