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

Serum Adipokines, Growth Factors, and Cytokines Are Independently Associated with Stunting in Bangladeshi Children

“…The stunted children in our study were comparatively more wasted and underweight than the comparison group, which could be another explanation of reduced cytokine production. Several studies reported marked deficits in IL-6, TNF-α, IL-1, and IFN-γ levels in malnourished children [45,46,47].…”

Differential gene expression in lymphocytes from malnourished children

“…These alterations could be related to the diminished cell proliferation and impaired immune response observed in malnourished children. Additionally, it is known that metaxin is required for TNF-induced apoptosis and necrosis (Wang et al, 2001); this is an important result because it has been reported that serum TNF (tumor necrosis factor) concentrations (Amesty et al, 2003) and absolute amounts of TNF secreted by cells (Azevedo et al, 2005) of severe malnourished children were higher than in well-nourished children. Therefore, the observed down-regulation of metaxin gene could be a mechanism of protection against TNF-induced apoptosis and necrosis in lymphocytes from malnourished children.…”

The Effect of Retinol Supplement on Blood Cytokine Concentrations in Children with Non-Severe Malaria Vivax

“…Some in vitro studies revealed that retinol had an effect on the TH1/TH2 balance, as evidenced by reduction of IFN -and TNF -secretion by TH1 cells or by promoting TH2 cells growth and differentiation to produce larger quantities of the IL-10 (Cantorna et al, 1994;Iwata et al, 2003). Vitamin A deficiency has been associated with an increase in TH1 response, intestinal parasitism and malnutrition (Jason et al, 2002;Azevedo et al, 2005). Furthermore, the prevalence of TH1 cytokines in children with malaria has been associated with severe anemia (Kurtzhals et al, 1999).…”