Increased production of tumor necrosis factor-alpha in whole blood cultures from children with primary malnutrition
Braz. j. med. biol. res
;
38(2): 171-183, fev. 2005. tab, graf
Article
in English
| LILACS, BVSAM
| ID: lil-393653
RESUMO
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 15 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.
Full text:
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Index:
LILACS (Americas)
Main subject:
Blood Cells
/
Leukocytes, Mononuclear
/
Child Nutrition Disorders
/
Lipopolysaccharides
/
Tumor Necrosis Factor-alpha
Type of study:
Observational study
Limits:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
2005
Type:
Article
Affiliation country:
Brazil
/
France
Institution/Affiliation country:
Département de l'Évaluation Scientifique de l'INSERM/FR
/
FIOCRUZ/BR
/
Institut Pasteur de Paris/FR
/
Universidade Federal do Rio de Janeiro/BR
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