Protein-energy malnutrition is associated with a decrease in immunity and an increase in infectious disease. Both of these effects are exacerbated in aging. Conversely, energy restriction (ER) without malnutrition extends the lifespan in animals and retards the age-related decline in various parameters of immune function. Recent evidence suggests, however, that aged ER mice exhibit an increased mortality in response to primary influenza infection compared with age-matched controls. Underweight may contribute to this outcome due to an inability to meet the energy demands associated with the immune response to primary viral infection. The energetic costs of immune responsiveness must be considered in the undernourished aging population and emerging studies of ER in humans.

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Energy restriction (ER) without malnutrition extends lifespan in mice and postpones age-related changes in immunity. However, we have previously shown that aged (22 mo old) ER mice exhibit increased mortality, impaired viral clearance, and reduced natural killer (NK) cell cytotoxicity following influenza infection compared with aged mice that consumed food ad libitum (AL). To determine whether the detrimental effects of ER in response to influenza infection occur independently of advanced age, young adult (6 mo) male C57BL/6 mice consuming an AL or ER diet were infected with influenza A virus (H1N1, PR8). Young adult ER mice exhibited increased mortality (P < 0.05) and weight loss (P < 0.01) in response to infection. ER mice exhibited decreased total (P < 0.001) and NK1.1+ lymphocytes (P < 0.05) in lung and reduced influenza-induced NK cell cytotoxicity in both lung (P < 0.01) and spleen (P < 0.05). Importantly, the mRNA expression of interferon (IFN)alpha/beta (P < 0.05) was also reduced in the lungs of ER mice in response to infection, and in vitro stimulation of NK cells from ER mice with type I IFN resulted in cytotoxicity comparable to that in NK cells from AL mice. In contrast, NK cell activation was enhanced in ER mice, determined as an increase in the percentage of NK cells expressing B220 (P < 0.001) and increased intracellular production of IFNgamma (P < 0.01). These data describe an age-independent and detrimental effect of ER on the innate immune response to influenza infection and suggest that a decrease in NK cell number and alterations in the NK cell-activating environment may contribute to decreased innate immunity in ER mice.

Natural Eggshell Membrane (NEM®) is a new novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy articular cartilage and the surrounding synovium.

Background: A partially hydrolysed and dried product of pacific whiting fish is currently marketed as a health food supplement to support ''intestinal health''. However, there has been only limited scientific study regarding its true biological activity. Aims: We therefore tested its efficacy in a variety of models of epithelial injury and repair. Methods: Effects on proliferation were determined using [ 3 H] thymidine incorporation into epithelial rat intestinal RIE-1 and human colonic HT29 cells. Effects on restitution (cell migration) were analysed using wounded HT29 monolayers and its ability to influence gastric injury analysed using a rat indomethacin restraint model. Partial characterisation of bioactive agents was performed using mass spectroscopy, high pressure liquid chromatography, and gas chromatography. Results: Both cell proliferation and cell migration were increased by about threefold when added at 1 mg/ml (p,0.01). Gastric injury was reduced by 59% when gavaged at 25 mg/ml (p,0.05), results similar to using the potent cytoprotective agent epidermal growth factor at 12.5 mg/ml. The vast majority of biological activity was soluble in ethanol, with glutamine in its single, di-, and tripeptide forms probably accounting for approximately 40% of the total bioactivity seen. Fatty acid constituents may also have contributed to cell migratory activity. Conclusions: Fish protein hydrolysate possesses biological activity when analysed in a variety of models of injury and repair and could provide a novel inexpensive approach for the prevention and treatment of the injurious effects of non-steroidal anti-inflammatory drugs and other ulcerative conditions of the bowel. Further studies appear justified. N atural medicinal products have been used for millennia for the treatment of multiple ailments. Although many have been superseded by conventional pharmaceutical approaches, there is currently a resurgence of interest in the use of natural bioactive products by the general public, with many healthy subjects and patients taking them for the prevention and treatment of multiple conditions, including gastrointestinal disorders.1 Unfortunately, current evidence of the scientific validity of many of these traditional and commercial compounds is severely limited.Fermentation is a commonly used process in the standard food industry as well as in the bioactive food (nutriceutical) field. Fermented food products include those derived from milk (yogurt, cheese, kefir), soy (natto, miso), fruits (wine), vegetables (sauerkraut), and fish and meats. All have been consumed for centuries for their nutritional or medicinal properties.2 Fermentation of fish and meat was introduced as a means of preservation, and fish sauces and pastes are staples or condiments in Southeast Asian, Scandinavian, and Eskimo cultures. Fermentation of food products has many effects, including partial degradation of protein constituents which, as well as aiding absorption from the gut, may also influence its biological activity.In the current study,...

SummaryComplex regional pain syndrome (CRPS) is a chronic pain disorder. Although its pathophysiology is not completely understood, neurogenic inflammation is thought to play a significant role. Microglia and astrocytes are activated following tissue injury or inflammation and have been reported to be both necessary and sufficient for enhanced nociception. Blood-borne monocytes/ macrophages can infiltrate the central nervous system (CNS) and differentiate into microglia resulting in hypersensitivity and chronic pain. The primary aim of this study was to evaluate the proportion of the proinflammatory CD14 + CD16 + monocytes as well as plasma cytokine levels in blood from CRPS patients compared to age-and gender-matched healthy control individuals. + CD16 + monocytes became elevated prior to or after developing CRPS. In either case, the elevation of blood proinflammatoty monocytes prior to the initiating event may predispose individuals for developing the syndrome whereas the elevation of blood proinflammatory monocytes following the development of CRPS may be relevant for its maintenance. Further evaluation of the role the immune system plays in the pathogenesis of CRPS may aid in elucidating disease mechanisms as well as the development of novel therapies for its treatment.

The emergence of H5N1 avian influenza and the threat of new or adapted viruses in bioterrorism have created an urgent interest in identifying agents to enhance the immune response to primary virus infection. Active hexose correlated compound (AHCC) is a natural mushroom extract reported to increase natural killer (NK) cell activity, survival, and bacterial clearance in young mice. However, the effects of AHCC on the response to viral infections have not been studied. In this study, young C57BL/6 mice were supplemented with 1 g AHCC/(kg body weight x d) for 1 wk prior to and throughout infection with influenza A (H1N1, PR8). Supplementation increased survival, decreased the severity of infection, and shortened recovery time following intranasal infection with flu, as determined by the recovery of body weight and epithelial integrity in the lungs. AHCC increased NK activity in lungs at d 1 (P < 0.05) and d 4 (P < 0.01) and in the spleen at d 2 postinfection (P < 0.01). Supplementation increased the percentage (P < 0.05) and number (P < 0.01) of NK1.1+ cells in the lung and reduced the infiltration of lymphocytes and macrophages compared with controls (P < 0.01). These data suggest that AHCC supplementation boosts NK activity, improves survival, and reduces the severity of influenza infection in young mice. Bolstering innate immunity with dietary bioactives may be one avenue for improving the immune response to primary flu infection.