In vitro anti-inflammatory effects of citrulline on peritoneal macrophages in Zucker diabetic fatty rats.
In type 2 diabetes (T2D) macrophage dysfunction increases susceptibility to infection and mortality. This may result from the associated decreased plasma concentration of arginine, an amino acid that plays an important role in immunity. In vitro, increasing arginine availability leads to an improvement in macrophage function; however, arginine supplementation in diabetic obese patients may be detrimental. The aim of the present study was to assess in vitro whether citrulline, an arginine precursor, could replace arginine in the regulation of macrophage function under a condition of diabetes and obesity. Peritoneal macrophages from diabetic obese or lean rats were incubated for 6 h in an arginine-free medium, in the presence of increasing citrulline concentrations (0·1, 0·5, 1 or 2 mmol/l). Cytokine and NO production was determined. Peritoneal macrophages from either lean or diabetic obese rats produced NO, and at higher levels in the cells from lean rats. In diabetic obese rats, TNF-α production decreased with increasing citrulline concentrations, but was higher than that in the cells from lean rats. In contrast, IL-6 production increased with increasing citrulline concentrations. The present experiment shows that citrulline is effectively used for NO production and regulates cytokine production in macrophages from diabetic obese rats. This effect warrants in vivo evaluation in T2D-related inflammation.
Laboratoire de Biologie de la Nutrition, EA 4466, Faculté de Pharmacie, Université Paris Descartes,Sorbonne Paris Cité,Paris,France.
Charlotte
C
Breuillard
Laboratoire de Biologie de la Nutrition, EA 4466, Faculté de Pharmacie, Université Paris Descartes,Sorbonne Paris Cité,Paris,France.
Sandra
S
Bonhomme
Laboratoire de Biologie de la Nutrition, EA 4466, Faculté de Pharmacie, Université Paris Descartes,Sorbonne Paris Cité,Paris,France.
Rémy
R
Couderc
Laboratoire de Biologie de la Nutrition, EA 4466, Faculté de Pharmacie, Université Paris Descartes,Sorbonne Paris Cité,Paris,France.
Luc
L
Cynober
Laboratoire de Biologie de la Nutrition, EA 4466, Faculté de Pharmacie, Université Paris Descartes,Sorbonne Paris Cité,Paris,France.
Jean-Pascal
JP
De Bandt
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001120:Arginine / Q000737:chemistry / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002956:Citrulline / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D015850:Interleukin-6 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D011924:Rats, Zucker; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine
Citrulline; Cytokines; Diabetes; Peritoneal macrophages