title: Effect of L-arginine supplementation on immune responsiveness in patients with sickle cell disease.
abstract: BACKGROUND
  L-arginine (L-Arg) is deficient in sickle cell disease (SSD) during vasoocclusion. We investigated possible causal relationship between L-Arg deficiency and immune dysfunction in SSD in steady-state.
  
  
  METHODS
  Fifteen patients with SSD in steady-state and 13 controls were studied. Plasma L-Arg levels were measured using liquid chromatography. T cell subsets and CD3zeta (CD3zeta) chain expression were analyzed using flow cytometry. Lymphocyte proliferative response to phytohemagglutinin (PHA) and production of IL-6 and interferon-gamma (IFN-gamma) were evaluated with and without L-Arg.
  
  
  RESULTS
  SSD patients had significantly lower L-Arg levels than controls. CD3 and CD19 cell populations were comparable for both groups, but SSD patients had above normal numbers of natural killer cells (P = 0.06). Patients and controls exhibited significantly increased lymphocyte blastogenesis to PHA after introduction of L-Arg to cultures; response of patients was significantly greater than values for control individuals. Proliferative response to candida in SSD patients was significantly lower than in controls; L-Arg supplementation did not increase this response. L-Arg had no effect on blastogenic response to PPD and candida albicans. No effect was likewise seen in production of IL-6 and IFN-gamma after addition of L-Arg. CD3zeta chain expression increased after addition of L-Arg in both groups; differences were insignificant.
  
  
  CONCLUSIONS
  L-Arg levels in steady-state SSD are significantly lower than in controls. L-Arg supplementation enhanced lymphocyte blastogenesis to PHA for both controls and patients, but not in response to antigen. There were no significant differences in CD3zeta chain expression although upregulation of expression occurred after L-Arg supplementation for both groups.
authors.affiliation: Department of Pediatrics, Pediatric Hematology/Oncology, Louisiana State University Health Sciences Centers (LSUHC-NO), New Orleans, Louisiana, USA.
authors.forename: Arnette
authors.initials: A
authors.lastname: Scavella
authors.forename: Lily
authors.initials: L
authors.lastname: Leiva
authors.forename: Hanh
authors.initials: H
authors.lastname: Monjure
authors.forename: Arnold H
authors.initials: AH
authors.lastname: Zea
authors.forename: Renee V
authors.initials: RV
authors.lastname: Gardner
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000276:immunology*; D001120:Arginine / Q000097:blood / Q000172:deficiency / Q000494:pharmacology*; D017252:CD3 Complex / Q000096:biosynthesis; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000473:pathology*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D010835:Phytohemagglutinins; D001120:Arginine