Sepsis: an arginine deficiency state?
OBJECTIVE
Sepsis is a major health problem considering its significant morbidity and mortality rate. The amino acid L-arginine has recently received substantial attention in relation to human sepsis. However, knowledge of arginine metabolism during sepsis is limited. Therefore, we reviewed the current knowledge about arginine metabolism in sepsis.


METHODS
This review summarizes the literature on arginine metabolism both in general and in relation to sepsis. Moreover, arginine-related therapies are reviewed and discussed, which includes therapies of both nitric oxide (NO) and arginine administration and therapies directed toward inhibition of NO.


METHODS
In sepsis, protein breakdown is increased, which is a key process to maintain arginine delivery, because both endogenous de novo production from citrulline and food intake are reduced. Arginine catabolism, on the other hand, is markedly increased by enhanced use of arginine in the arginase and NO pathways. As a result, lowered plasma arginine levels are usually found. Clinical symptoms of sepsis that are related to changes in arginine metabolism are mainly related to hemodynamic alterations and diminished microcirculation. NO administration and arginine supplementation as a monotherapy demonstrated beneficial effects, whereas nonselective NO synthase inhibition seemed not to be beneficial, and selective NO synthase 2 inhibition was not beneficial overall.


CONCLUSIONS
Because sepsis has all the characteristics of an arginine-deficiency state, we hypothesise that arginine supplementation is a logical option in the treatment of sepsis. This is supported by substantial experimental and clinical data on NO donors and NO inhibitors. However, further evidence is required to prove our hypothesis.
Luiking
Yvette C
YC
Maastricht University/Hospital, Department of Surgery, Nutrition and Toxicology Research Institute, Maastricht, The Netherlands.
Poeze
Martijn
M
Dejong
Cornelis H
CH
Ramsay
Graham
G
Deutz
Nicolaas E
NE
D001120:Arginine / Q000172:deficiency* / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D018805:Sepsis / Q000378:metabolism* / Q000628:therapy
D009569:Nitric Oxide; D001120:Arginine