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Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
Published on: September 16, 2017
Circulating and mitogen-induced tumor necrosis factor (TNF) in malnourished children
A Giovambattista1, E Spinedi, A Sanjurjo
1Unidad de Neuroendocrinología, Instituto Multidisciplinario de Biología Celular (CIC-CONICET), La Plata.
Insights
Malnourished children exhibit elevated basal tumor necrosis factor (TNF) but reduced in vitro TNF production by leukocytes. These immune dysfunctions in protein energy malnutrition (PEM) may increase infection risk.
Area of Science:
- Immunology
- Pediatrics
- Nutrition Science
Background:
- Protein energy malnutrition (PEM) in children is linked to heightened infection risk and mortality.
- PEM is associated with inflammatory-immune response abnormalities, including altered cytokine production.
- These immune deficits may explain the increased susceptibility and severity of infections in malnourished children.
Purpose of the Study:
- To investigate basal serum concentrations of tumor necrosis factor (TNF) in children with PEM.
- To correlate these TNF levels with serum cortisol and plasma corticotrophin.
- To assess the in vitro production of TNF by peripheral blood leukocytes (PBL) in PEM.
Main Methods:
- Comparison of basal plasma corticotrophin and serum cortisol levels between malnourished and well-nourished children.
- Measurement of basal serum TNF concentrations in both groups.
- Assessment of mitogen-induced TNF production by PBL in vitro from malnourished and control children.
Main Results:
- No significant differences were observed in basal plasma corticotrophin or serum cortisol levels between malnourished and control children.
- Basal serum TNF concentrations were significantly higher in malnourished children compared to controls.
- Mitogen-induced in vitro TNF production by PBL was significantly reduced in children with PEM.
Conclusions:
- Children with PEM display abnormal circulating and inducible TNF production, independent of elevated cortisol levels.
- These TNF dysregulations may impact the immune response to infections in malnourished children.
- Further research is warranted to understand the clinical implications of these immune alterations in PEM.
Abstract:
Malnutrition in children is associated with an increased risk of infection and death. Multiple abnormalities in the inflammatory-immune response, including cytokine production, have been described in protein energy malnourished (PEM) children and could account for increased severity and frequency of infection. The aim of the present study was to determine whether there are abnormal basal tumor necrosis factor (TNF) serum concentrations in PEM children, to relate it with serum cortisol and plasma corticotrophin levels and to explore simultaneously the in vitro production of TNF by peripheral blood leukocytes (PBL). No differences were found in basal plasma corticotrophin and serum cortisol concentrations in malnourished as compared with normal, well-nourished control children. Basal TNF serum concentrations were significantly higher in malnourished children than in controls. Conversely, mitogen induced TNF production by PBL in vitro was significantly reduced in PEM children compared with controls. Abnormalities in circulating and mitogen-induced TNF production are present in malnourished children even in absence of elevated serum cortisol concentrations. These abnormalities potentially could modify inflammatory-immune responses to infectious stimuli in malnourished children.
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