title: Increased production of tumor necrosis factor-alpha in whole blood cultures from children with primary malnutrition.
abstract: Because low tumor necrosis factor-alpha (TNF-alpha) production has been reported in malnourished children, in contrast with high production of TNF-alpha in experimental protein-energy malnutrition, we reevaluated the production of TNF-alpha in whole blood cultures from children with primary malnutrition free from infection, and in healthy sex- and age-matched controls. Mononuclear cells in blood diluted 1:5 in endotoxin-free medium released TNF-alpha for 24 h. Spontaneously released TNF-alpha levels (mean +/- SEM), as measured by enzyme immunoassay in the supernatants of unstimulated 24-h cultures, were 10,941 +/- 2,591 pg/ml in children with malnutrition (N = 11) and 533 +/- 267 pg/ml in controls (N = 18) (P < 0.0001). TNF-alpha production was increased by stimulation with lipopolysaccharide (LPS), with maximal production of 67,341 +/- 16,580 pg/ml TNF-alpha in malnourished children and 25,198 +/- 2,493 pg/ml in controls (P = 0.002). In control subjects, LPS dose-dependently induced TNF-alpha production, with maximal responses obtained at 2000 ng/ml. In contrast, malnourished patients produced significantly more TNF-alpha with 0.02-200 ng/ml LPS, responded maximally at a 10-fold lower LPS concentration (200 ng/ml), and presented high-dose inhibition at 2000 ng/ml. TNF-alpha production a) was significantly influenced by LPS concentration in control subjects, but not in malnourished children, who responded strongly to very low LPS concentrations, and b) presented a significant, negative correlation (r = -0.703, P = 0.023) between spontaneous release and the LPS concentration that elicited maximal responses in malnourished patients. These findings indicate that malnourished children are not deficient in TNF-alpha production, and suggest that their cells are primed for increased TNF-alpha production.
authors.affiliation: Departamento de Pediatria e Laboratório de Fisiopatologia Humana, Instituto Fernandes Figueira, FIOCRUZ, Rio de Janeiro, RJ, Brazil. zina_maria@uol.com.br
authors.forename: Z M A
authors.initials: ZM
authors.lastname: Azevedo
authors.forename: R A
authors.initials: RA
authors.lastname: Luz
authors.forename: S H
authors.initials: SH
authors.lastname: Victal
authors.forename: B
authors.initials: B
authors.lastname: Kurdian
authors.forename: V M
authors.initials: VM
authors.lastname: Fonseca
authors.forename: C
authors.initials: C
authors.lastname: Fitting
authors.forename: F P
authors.initials: FP
authors.lastname: Câmara
authors.forename: N
authors.initials: N
authors.lastname: Haeffner-Cavaillon
authors.forename: J-M
authors.initials: JM
authors.lastname: Cavaillon
authors.forename: M I C
authors.initials: MI
authors.lastname: Gaspar Elsas
authors.forename: P
authors.initials: P
authors.lastname: Xavier Elsas
mesh_terms: D001773:Blood Cells / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D015362:Child Nutrition Disorders / Q000097:blood* / Q000276:immunology; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha