Cytokine response in malnutrition.
|Publication:||Name: Indian Journal of Medical Research Publisher: Indian Council of Medical Research Audience: Academic Format: Magazine/Journal Subject: Biological sciences; Health Copyright: COPYRIGHT 2009 Indian Council of Medical Research ISSN: 0971-5916|
|Issue:||Date: July, 2009 Source Volume: 130 Source Issue: 1|
|Topic:||Event Code: 310 Science & research|
|Geographic:||Geographic Scope: India Geographic Code: 9INDI India|
The World Health Organization defines malnutrition as "the
cellular imbalance between supply of nutrients and energy and the
body's demand for them to ensure growth, maintenance, and specific
functions (1). It has been recognized that malnutrition is the most
common cause of immunodeficiency worldwide (2). Actually, malnutrition
and infection interact in a vicious cycle and the presence of one easily
leads to the development of the other (3). There are several mechanisms
involved in this relationship. Protein energy malnutrition (PEM) impairs
cell-mediated immunity, phagocytic function, and the complement system.
It also diminishes immunoglobulin (igA, IgM, and IgG) concentrations and
cytokine production (3). Micronutrient deficiencies associated with PEM
also adversely affect the immune response.
In response to infection, the immune system first executes innate and then subsequently acquired host defense functions of high diversity. Both processes involve activation and propagation of immune cells and synthesis of an array of molecules requiring DNA replication, RNA expression and protein synthesis and secretion, and therefore consume additional anabolic energy. Mediators of inflammation further increase the catabolic response. Nutritional status of the host critically determines the outcome of infection. PEM is a common cause of secondary immune deficiency and susceptibility to infection in humans. Apart from deficiencies in single nutrients, such as vitamins, essential fatty acids, amino acids, iron, and trace elements, undemutrition greatly increases susceptibility to infectious diseases, especially in children belonging to the lower socio-economic strata (4). Malnutrition is responsible, directly or indirectly, for 54 per cent of the 10.8 million deaths per year in under-five children and contributes to every second death (53%) associated with infectious diseases in developing countries (5). Infection causes energy loss on the part of the individual, which reduces productivity on the community level and perpetuates the alarming spiral of malnutrition, infection, disease, and poverty. Severe malnutrition during childhood affects thymic development, which compromises immunity in children by a long-term reduction of peripheral lymphocyte counts (6). This immunodeficiency represents a key factor in susceptibility to infections and has therefore been termed nutritionally acquired immunodeficiency syndrome (7). In severely malnourished patients, both acquired immunity like lymphocyte functions as well as innate host defense mechanisms like macrophages and granulocytes are affected. Diminished immune functions render undernourished patients more susceptible to infections. In addition to promoting acute and chronic infections, PEM impairs the linear growth of children, leading to a further reduction in food intake, nutrient absorption, direct and catabolic nutrient losses and increased metabolic requirements. Acute phase response and pro-inflammatory cytokines can directly affect the bone remodelling required for longitudinal growth (8). Stimulation of an immune response by infection increases the demand for energy and associated substrates, leading to a vicious cycle of adverse nutritional status and increased susceptibility to infection. Inflammatory conditions such as mediators of sepsis increase the catabolic disease state.
Cytokines are substances that play an important role in coordinating the inflammatory response of the body to various external and internal stimuli (9). There are two classes of cytokines: Pro-inflammatory and anti-inflammatory. The pro-inflammatory cytokines are essential to initiate defense against various pathogens. In certain conditions, there is overproduction of the pro-inflammatory cytokines resulting in counter-productive effects. The anti-inflammatory cytokines down-regulate the inflammatory process by suppressing production of the pro-inflammatory cytokines and help to balance the inflammatory response. Similarly excess secretion of anti-inflammatory cytokines may have deleterious effects on organ function. The pro-inflammatory cytokines include IL-1[beta], IL-6, IL-8, TNF-[alpha], and IL-2, and the anti-inflammatory cytokines include IL-1 receptor antagonist, IL-4, IL-10, and IL-13.
In the context of what is known as the 10/90 gap areas, i.e., 10 per cent of global health research funding is being targeted to health problems that account for 90 per cent of the global disease burden and hence, research on infection and malnutrition is highly warranted for scientific, economic, and ethical reasons (10,11) To conquer malnutrition, cost-efficient and practical approaches need to be established. Measures to counteract acute malnutrition and immunosuppression are the need of the hour.
Usually children with severe malnutrition are hospitalized under such circumstances and given milk products as therapeutic food. It has been shown that addition of curd/yogurt and leaf protein concentrate (LPC) can be beneficial in tackling the problem of malnutrition and in improving immunity and achieving immunomodulation (12). It has also been shown that cytokines (TNF[alpha], IFN[gamma], IL-10, IL-4) may serve as biological markers to assess the effect of functional foods like curd or LPC on immunity in malnutrition. Curd and LPC may help to maintain the balance in cytokine production in malnourished children by increasing the production of pro-inflammatory and anti-inflammatory cytokines as shown by Dewan et al (13) in this issue. The use of such cheap and locally available items can go a long way in improving survival and also adding quality to survival.
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(12.) Diwan P, Kaur I, Chattopadhya D, Faridi MMA, Agarwal KN. A pilot study on the effects of curd (dahi) and leaf protein concentrate in children with protein energy malnutrition. Indian J Med Res 2007; 126 : 199-203.
(13.) Dewan Pooja, Kaur IR, Faridi MMA, Agarwal KN. Cytokine response to dietary rehabilitation with curd (Indian dahi) and leaf protein concentrate in malnourished children, Indian J Med Res 2009; 130 : 31-6.
Department of Pediatrics
SAT Hospital, Govt. Medical College
Thiruvananthapuram 695 011, India
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