Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor (TNF, cachectin), a cytokine secreted by macrophages and T-cells, mediates inflammatory and immune responses, and is associated with wasting in persons with malignancies or AIDS. In inflammation, TNF attracts and activates neutrophils, stimulating phagocytic function of neutrophils and macrophages. TNF also increases hepatic cell resistance to damaging parasitic effects; enhances endothelial permeability, causing edema; aids in wound healing by stimulating tissue and vascular growth; enhances lymphocytic activity through cytokine activation; acts with interleukin (IL) to produce fever, anorexia, lethargy and sleep; and possesses antitumor activity, particularly against the presumed origin of Kaposi's sarcoma, capillary endothelial cells. The host has an acute phase response (APR) following TNF- and IL-induced immunologic activation. TNF and IL decrease production and activity of lipoprotein lipase (LPL), resulting in reduced uptake and improper storage of fat; and they stimulate anabolism of fatty acids, causing hypertriglyceridemia. This "futile cycling" causes shuttling of fatty acids between adipose tissue and the liver, and use of muscle protein as the main fuel source. This, along with further muscular breakdown due to the increased caloric demands of fever, may affect cachexia. TNF benefits the HIV-infected through selective killing of HIV-infected cells, although effects may be dose and time dependent. The negative effects of TNF may be impeded by anti-cytokine therapy. Possible therapies include dietary N-3 fatty acid (fish oil), an inhibitor of TNF and IL production in vitro; pentoxifylline (Trental), another TNF production inhibitor; anti-TNF monoclonal antibodies; and soluble TNF receptors.
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PMID:Tumor necrosis factor: its role in HIV/AIDS. 1136 96

Immune system activation begins a host of physiological responses. Infectious agents are recognized by monocytes and macrophages which in turn stimulate cytokine production. It is the hormone-like factors called cytokines that orchestrate the immune response. The classic responses observed with immune system activation and cytokine production include: anorexia, fever, lethargy, recruitment of other immune cells, and phagocytosis. While production of immune system components is known to require some amino acids, increases in amino acid requirements are more than offset by the associated decrease in protein accretion and increased muscle protein degradation that also accompanies immune system activation. However, the biggest impact of cytokine production is a decrease in feed intake. Therefore, as feed intake decreases, the energy needed to drive protein synthesis is also decreased. This suggests that diets should still be formulated on a similar calorie:lysine ratio as those formulated for non-immune challenged pigs. The evidence is sparse or equivocal for increasing nutrient requirements during an immune challenge. Nutritionists and swine producers should resist the pressure to alter the diet, limit feed, or add expensive feed additives during an immune challenge. While immune stimulation does not necessitate changes in diet formulation, when pigs are challenged with non-pathogenic diarrhea there are potential advantages on gut health with the increased use of crystalline amino acids rather than intact protein sources (i.e., soybean meal). This is because reducing crude protein decreases the quantity of fermentable protein entering the large intestine, which lowers post weaning diarrhea. It also lowers the requirement for expensive specialty protein sources or other protein sources such as soybean meal that present immunological challenges to the gut. The objective of this review is two-fold. The first is to discuss immunity by nutrition interactions, or lack thereof, and secondly, to review amino acid requirement estimates for nursery pigs.
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PMID:Practical starter pig amino acid requirements in relation to immunity, gut health and growth performance. 2453 55