Nutritional modulation of the innate immune response to influenza infection

Natural killer (NK) cells play an important role in controlling virus infections and provide a potential target for nutritional modulations that may alter the innate immune response to viruses. Data presented here provide direct evidence that 1) NK cells limit influenza virus in the lung early following infection, 2) an age-associated defect in inducible NK cell cytotoxicity contributes to the increased susceptibility of aged mice to primary influenza infection, and 3) NK cells respond, both positively and negatively, to nutritional interventions. Caloric restriction (CR) is a nutritional intervention that has been shown to extend lifespan in mice and postpone age-related changes in immunity. However, in our studies, aged (22 mo) CR mice exhibited increased mortality, impaired viral clearance, and reduced natural killer (NK) cell activity following influenza infection compared to aged ad-libitum (AL) mice. To determine if these detrimental effects of CR occur independently of advanced age, young adult (6 mo) CR and AL C57BL/6 mice were infected with 104 TCID50/100 HAU of influenza A virus (H1N1, PR8). The CR mice exhibited increased mortality (P<0.05), weight loss (P<0.01), lung virus titers (P<0.05), and lung pathology (P<0.001) compared to young AL controls. Also, CR mice exhibited a decrease in total (P<0.001) and NK1.1+ lymphocytes (P<0.05) compared to AL in response to infection, as well as a reduction in influenza-induced NK cell cytotoxicity in both lung (P<0.01) and spleen (P<0.05). These data are the first to describe an age-independent and detrimental effect of CR on the innate immune response to influenza infection. In a separate study, young (6-8wk) C57BL/6 mice were supplemented with 1g/kg body weight of active hexose correlated compound (AHCC), a fermented mushroom extract, for 7 days prior to and throughout infection with 100 HAU of influenza A virus (H1N1, PR8). Supplementation increased survival and decreased weight loss (P<0.001) in response to influenza infection. Further, supplementation increased NK cell activity in lung at 1 day p.i. (P<0.05) and 4 days p.i. (P<0.01) and in spleen at 2 days p.i. (P<0.01). In conclusion, NK cells are important in controlling primary influenza infection, and both aging and nutritional status alter this response.Ph.D., Life Sciences -- Drexel University, 200

Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the knee: a randomized, multicenter, double-blind, placebo-controlled clinical study

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. The randomized, multicenter, double-blind, placebo-controlled Osteoarthritis Pain Treatment Incorporating NEM® clinical study was conducted to evaluate the efficacy and safety of NEM® as a treatment for pain and stiffness associated with osteoarthritis of the knee. Sixty-seven patients were randomly assigned to receive either oral NEM® 500 mg (n = 34) or placebo (n = 33) daily for 8 weeks. The primary endpoint was the change in overall Western Ontario and McMasters Universities (WOMAC) Osteoarthritis Index as well as pain, stiffness, and function WOMAC subscales measured at 10, 30, and 60 days. The clinical assessment was performed on the intent-to-treat population. Supplementation with NEM® produced an absolute rate of response that was statistically significant (up to 26.6%) versus placebo at all time points for both pain and stiffness, but was not significantly improved for function and overall WOMAC scores, although trending toward improvement. Rapid responses were seen for mean pain subscores (15.9% reduction, P = 0.036) and mean stiffness subscores (12.8% reduction, P = 0.024) occurring after only 10 days of supplementation. There were no serious adverse events reported during the study and the treatment was reported to be well tolerated by study participants. Natural Eggshell Membrane (NEM®) is an effective and safe option for the treatment of pain and stiffness associated with knee osteoarthritis. Supplementation with NEM®, 500 mg taken once daily, significantly reduced both joint pain and stiffness compared to placebo at 10, 30, and 60 days. The Clinical Trial Registration number for this study is NCT00750477

Dendritic Cells Are Required for Optimal Activation of Natural Killer Functions following Primary Infection with Herpes Simplex Virus Type 1▿

Natural killer (NK) cells play an important role in the optimal clearance of herpes simplex virus type 1 (HSV-1) infection in mice. Activated NK cells function via cytokine secretion or direct cytolysis of target cells; dendritic cells (DCs) are thought to make critical contributions in the activation of both of these functions. Yet, the magnitude and physiological relevance of DC-mediated NK cell activation in vivo is not completely understood. To examine the contribution of DC help in regulating NK cell functions after infection with HSV-1, we utilized a transgenic mouse model that allows the transient ablation of DCs. Using this approach, it was found that the gamma interferon (IFN-γ) expression potential of NK cells is quantitatively and qualitatively impaired in the absence of DCs. With regard to priming of NK cytolytic functions, the ablation of DCs did not significantly affect cytotoxic protein expression by NK cells. An in vivo cytolytic assay did, however, reveal impairments in the magnitude of NK cell cytotoxicity. Overall, this study provides direct evidence that functional DCs are required for optimal IFN-γ expression and cytolytic function by NK cells following infection with HSV-1