title: The dose-dependent immunoregulatory effects of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester in rats with sub-acute peritonitis.
abstract: BACKGROUND
  Chronic inflammation accompanied by arginine deficiency, immune dysfunction, and excess nitric oxide (NO) production is a clinical condition found in patients with peritonitis. A previous study showed that the nonselective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) may facilitate the metabolism of the immune nutrient arginine without altering NO homeostasis in rats with sub-acute peritonitis. Here, we investigated the effects of L-NAME on the immunocytic subpopulation distribution and response.
  
  
  METHODS
  Male Wistar rats with cecal puncture-induced peritonitis were administered parenteral nutrition solutions supplemented with 0 (CPP group), 5 (LNA group), 25 (MNA group) or 50 (HNA group) mg · kg(-1) · day(-1) of L-NAME for 7 days. Parenteral-fed sham-operated rats (TPN group) and orally-fed healthy rats (R group) were included as controls.
  
  
  RESULTS
  The TPN group had significantly increased spleen weights and levels of plasma nitrite/nitrate (NOx), circulating white blood cells (WBC), and splenocytic T cells, as well as significantly decreased levels of cytotoxic T- and B-leukocytes and B-splenocytes compared to the R group. The CPP group had significantly decreased levels of plasma NOx and concanavalin (Con) A-stimulated interferon (IFN)-γ and interleukin (IL)-2 production by leukocytes and significantly increased production of Con A-stimulated tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS)-stimulated IFN-γ in the leukocytes. In addition, the LNA and MNA groups had significantly decreased spontaneous IL-6 and Con A-stimulated TNF-α and IFN-γ production by the leukocytes while the HNA group had significantly increased LPS-stimulated TNF-α and Con A-stimulated IFN-γ and IL-2 production by the splenocytes compared to the CPP group.
  
  
  CONCLUSIONS
  Low-dose L-NAME infusion may suppress proinflammatory and T-helper-1 (Th1) response in leukocytes, and high-dose infusion may activate the proinflammatory response in splenic macrophages and Th1 response in T-splenocytes in rats with sub-acute peritonitis.
authors.affiliation: Department of Pediatrics, Clinical Nutrition Support Service Team, Changhua Christian Hospital, Changhau, Taiwan.
authors.forename: Chien-Chou
authors.initials: CC
authors.lastname: Hsiao
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Lee
authors.forename: Lon-Yen
authors.initials: LY
authors.lastname: Tsao
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Lo
mesh_terms: D000208:Acute Disease; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D007263:Infusions, Parenteral; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D010288:Parenteral Nutrition; D010538:Peritonitis / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; C026512:arginine methyl ester; C002744:3-nitrotyrosine; D014443:Tyrosine; D001120:Arginine; D019001:Nitric Oxide Synthase