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Acute-phase protein response to infection in severe malnutrition
J F Morlese1, T Forrester, F Jahoor
1United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Insights
Severely malnourished children can mount an acute-phase protein (APP) response during infection, but not for all proteins like fibrinogen. This response is achieved through varied mechanisms, not solely increased synthesis rates.
Area of Science:
- Biochemistry
- Pediatric Nutrition
- Immunology
Background:
- The capacity of malnourished infants to mount an acute-phase protein (APP) response to infection is not well understood.
- It remains unclear if this response involves increased synthesis rates of APPs in malnourished children.
Purpose of the Study:
- To investigate the acute-phase protein (APP) response in infected, malnourished children.
- To determine if the APP response is mediated by increased APP synthesis rates.
Main Methods:
- Measured plasma concentrations of five APPs (C-reactive protein, alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, fibrinogen).
- Determined synthesis rates of three APPs (alpha1-antitrypsin, haptoglobin, fibrinogen) using [2H3]leucine infusion.
- Studied nine infected marasmic children at different stages: acute infection, post-infection, and recovery.
Main Results:
- Plasma concentrations of most APPs were elevated during acute infection compared to recovery phases.
- Haptoglobin synthesis significantly increased during infection, while fibrinogen and alpha1-antitrypsin synthesis rates remained constant.
- The APP response in malnourished children involves diverse mechanisms, not solely elevated synthesis for all proteins.
Conclusions:
- Severely malnourished children can mount an APP response to infection, excluding fibrinogen.
- The APP response is achieved through varied mechanisms, highlighting the complexity of immune function in malnutrition.
- Findings contribute to understanding the nutritional and immunological challenges in severe childhood malnutrition.
Abstract:
It is not known whether malnourished infants can mount a comprehensive acute-phase protein (APP) response and, if so, whether this is achieved by increasing APP synthesis rates. To address these issues, we measured 1) the plasma concentrations of five APPs (C-reactive protein, alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, and fibrinogen) and 2) the synthesis rates of three APPs (alpha1-antitrypsin, haptoglobin, and fibrinogen) using a constant intragastric infusion of [2H3]leucine in nine infected marasmic children at approximately 2 days postadmission (study 1), approximately 9 days postadmission when infections had cleared (study 2), and approximately 59 days postadmission at recovery (study 3). Except for fibrinogen, the plasma concentrations of all APPs were higher in study 1 than in studies 2 and 3. Although the rate of synthesis of haptoglobin was significantly greater in study 1 than study 2, the rates of fibrinogen and alpha1-antitrypsin synthesis were similar in all three studies. These results show that 1) severely malnourished children can mount an APP response to infection which does not include fibrinogen and 2) the APP response is accomplished through different mechanisms.