Effects of aerobic exercise training on cerebral pulsatile hemodynamics in middle-aged adults with elevated blood pressure/stage 1 hypertension.

Mechanisms behind the protective effects of aerobic exercise on brain health remain elusive but may be vascular in origin and relate to cerebral pulsatility. This pilot study investigated the effects of 12-wk aerobic exercise training on cerebral pulsatility and its vascular contributors (large artery stiffness, characteristic impedance) in at-risk middle-aged adults. Twenty-eight inactive middle-aged adults with elevated blood pressure or stage 1 hypertension were assigned to either moderate/vigorous aerobic exercise training (AET) for 3 days/wk or no-exercise control (CON) group. Middle cerebral artery (MCA) pulsatility index (PI), large artery (i.e., aorta, carotid) stiffness, and characteristic impedance were assessed via Doppler and tonometry at baseline, 6, and 12 wk, whereas cardiorespiratory fitness (V̇o2peak) was assessed via incremental exercise test and cognitive function via computerized battery at baseline and 12 wk. V̇o2peak increased 6% in AET and decreased 4% in CON (P < 0.05). Proximal aortic compliance increased (P = 0.04, partial η2 = 0.14) and aortic characteristic impedance decreased (P = 0.02, partial η2 = 0.17) with AET but not CON. Cerebral pulsatility showed a medium-to-large effect size increase with AET, although not statistically significant (P = 0.07, partial η2 = 0.11) compared with CON. Working memory reaction time improved with AET but not CON (P = 0.02, partial η2 = 0.20). Our data suggest 12-wk AET elicited improvements in central vascular hemodynamics (e.g., proximal aortic compliance and characteristic impedance) along with apparent, paradoxical increases in cerebral pulsatile hemodynamics.NEW & NOTEWORTHY We identify differential central versus cerebrovascular responses to 12 wk of aerobic exercise training in middle-aged adults. Although proximal aortic compliance and characteristic impedance improved after 12 wk of exercise, cerebral pulsatility tended to unexpectedly increase. These data suggest short-term aerobic exercise training may lead to more immediate benefits in the central vasculature, whereas longer duration exercise training may be required for beneficial changes in pulsatility within the cerebrovasculature.

Aerobic, resistance, or combined exercise training and cardiovascular risk profile in overweight or obese adults: the CardioRACE trial.

BACKGROUND AND AIMS: To determine the comparative efficacy of resistance, aerobic, and combined resistance plus aerobic exercise on cardiovascular disease (CVD) risk profile. METHODS: This randomized controlled trial enrolled 406 adults aged 35-70 years with overweight or obesity and elevated blood pressure. Participants were randomly assigned to resistance (n = 102), aerobic (n = 101), combined resistance plus aerobic exercise (n = 101), or no-exercise control (n = 102). All exercise participants were prescribed 1 h of time-matched supervised exercise (the combination group with 30 min of each resistance and aerobic exercise) three times per week for 1 year. The primary outcome was the change from baseline to 1 year in the standardized composite Z-score of four well-established CVD risk factors: systolic blood pressure, low-density lipoprotein (LDL) cholesterol, fasting glucose, and per cent body fat. RESULTS: Among 406 participants (53% women), 381 (94%) completed 1-year follow-up. Compared with the control group, the composite Z-score decreased at 1 year, which indicates improved CVD risk profile, in the aerobic {mean difference, -0.15 [95% confidence interval (CI): -0.27 to -0.04]; P = .01} and combination [mean difference, -0.16 (95% CI: -0.27 to -0.04); P = .009] groups, but not in the resistance [mean difference, -0.02 (95% CI: -0.14 to 0.09); P = .69] group. Both aerobic and combination groups had greater reductions in the composite Z-score compared with the resistance group (both P = .03), and there was no difference between the aerobic and combination groups (P = .96). Regarding the four individual CVD risk factors, only per cent body fat decreased in all three exercise groups at 1 year, but systolic blood pressure, LDL cholesterol, and fasting glucose did not decrease in any exercise groups, compared with the control group. CONCLUSIONS: In adults with overweight or obesity, aerobic exercise alone or combined resistance plus aerobic exercise, but not resistance exercise alone, improved composite CVD risk profile compared with the control.

Novel nanoadjuvants balance immune activation with modest inflammation: implications for older adult vaccines.

BACKGROUND: Age-associated impairments of immune response and inflammaging likely contribute to poor vaccine efficacy. An appropriate balance between activation of immune memory and inflammatory response may be more effective in vaccines for older adults; attempts to overcome reduced efficacy have included the addition of adjuvants or increased antigenic dose. Next generation vaccine formulations may also use biomaterials to both deliver and adjuvant vaccine antigens. In the context of aging, it is important to determine the degree to which new biomaterials may enhance antigen-presenting cell (APC) functions without inducing potent inflammatory responses of APCs or other immune cell types (e.g., T cells). However, the effect of newer biomaterials on these cell types from young and older adults remains unknown. RESULTS: In this pilot study, cells from young and older adults were used to evaluate the effect of novel biomaterials such as polyanhydride nanoparticles (NP) and pentablock copolymer micelles (Mi) and cyclic dinucleotides (CDN; a STING agonist) on cytokine and chemokine secretion in comparison to standard immune activators such as lipopolysaccharide (LPS) and PMA/ionomycin. The NP treatment showed adjuvant-like activity with induction of inflammatory cytokines, growth factors, and select chemokines in peripheral blood mononuclear cells (PBMCs) of both young (n = 6) and older adults (n = 4), yet the degree of activation was generally less than LPS. Treatment with Mi or CDN resulted in minimal induction of cytokines and chemokine secretion with the exception of increased IFN-α and IL-12p70 by CDN. Age-related decreases were observed across multiple cytokines and chemokines, yet IFN-α, IL-12, and IL-7 production by NP or CDN stimulation was equal to or greater than in cells from younger adults. Consistent with these results in aged humans, a combination nanovaccine composed of NP, Mi, and CDN administered to aged mice resulted in a greater percentage of antigen-specific CD4+ T cells and greater effector memory cells in draining lymph nodes compared to an imiquimod-adjuvanted vaccine. CONCLUSIONS: Overall, our novel biomaterials demonstrated a modest induction of cytokine secretion with a minimal inflammatory profile. These findings suggest a unique role for biomaterial nanoadjuvants in the development of next generation vaccines for older adults.

"Just right" combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation.

BACKGROUND: The loss in age-related immunological markers, known as immunosenescence, is caused by a combination of factors, one of which is inflammaging. Inflammaging is associated with the continuous basal generation of proinflammatory cytokines. Studies have demonstrated that inflammaging reduces the effectiveness of vaccines. Strategies aimed at modifying baseline inflammation are being developed to improve vaccination responses in older adults. Dendritic cells have attracted attention as an age-specific target because of their significance in immunization as antigen presenting cells that stimulate T lymphocytes. RESULTS: In this study, bone marrow derived dendritic cells (BMDCs) were generated from aged mice and used to investigate the effects of combinations of adjuvants, including Toll-like receptor, NOD2, and STING agonists with polyanhydride nanoparticles and pentablock copolymer micelles under in vitro conditions. Cellular stimulation was characterized via expression of costimulatory molecules, T cell-activating cytokines, proinflammatory cytokines, and chemokines. Our results indicate that multiple TLR agonists substantially increase costimulatory molecule expression and cytokines associated with T cell activation and inflammation in culture. In contrast, NOD2 and STING agonists had only a moderate effect on BMDC activation, while nanoparticles and micelles had no effect by themselves. However, when nanoparticles and micelles were combined with a TLR9 agonist, a reduction in the production of proinflammatory cytokines was observed while maintaining increased production of T cell activating cytokines and enhancing cell surface marker expression. Additionally, combining nanoparticles and micelles with a STING agonist resulted in a synergistic impact on the upregulation of costimulatory molecules and an increase in cytokine secretion from BMDCs linked with T cell activation without excessive secretion of proinflammatory cytokines. CONCLUSIONS: These studies provide new insights into rational adjuvant selection for vaccines for older adults. Combining appropriate adjuvants with nanoparticles and micelles may lead to balanced immune activation characterized by low inflammation, setting the stage for designing next generation vaccines that can induce mucosal immunity in older adults.

Mitochondrial Mass of Naïve T Cells Is Associated with Aerobic Fitness and Energy Expenditure of Active and Inactive Adults.

PURPOSE: Chronic exercise training is known to induce metabolic changes, but whether these adaptations extend to lymphocytes and how this may affect immune function remains largely unknown. This study was conducted to determine the extent to which mitochondrial characteristics of naïve T cells differ according to fitness status and to further examine the energy production pathways of cells from aerobically trained and inactive participants. METHODS: Blood was collected from 30 aerobically active (>6 h·wk -1 ) or inactive (<90 min·wk -1 ) men and women. Naïve T cell mitochondrial mass, membrane potential, and biogenesis were assessed with flow cytometry. Participants completed a treadmill maximal oxygen consumption (V̇O 2peak ) test and wore a physical activity monitor for 1 wk. In a subset of participants, naïve CD8 + T cell activation-induced glycolytic and mitochondrial ATP production was measured. RESULTS: Active participants exhibited 16.7% more naïve CD8 + T cell mitochondrial mass ( P = 0.046), 34% greater daily energy expenditure ( P < 0.001), and 39.6% higher relative V̇O 2peak ( P < 0.001), along with 33.9% lower relative body fatness ( P < 0.001). Among all participants, naïve CD8 + T cell mitochondrial mass was correlated with estimated energy expenditure ( r = 0.36, P = 0.048) and V̇O 2peak ( r = 0.47, P = 0.009). There were no significant differences in ATP production, mitochondrial biogenesis, or mitochondrial membrane potential between active and inactive groups. CONCLUSIONS: This is the first study to examine the effects of aerobic exercise training status on metabolic parameters within human naïve T cells. Findings suggest that mitochondrial adaptations in certain immune cell types are positively associated with aerobic fitness and energy expenditure. This study provides a foundation for future development of prophylactic and therapeutic interventions targeting specific immune cell subsets to improve the immune response and overall health.

Exercise after influenza or COVID-19 vaccination increases serum antibody without an increase in side effects.

Vaccination is an effective public health measure, yet vaccine efficacy varies across different populations. Adjuvants improve vaccine efficacy but often increase reactogenicity. An unconventional behavioral "adjuvant" is physical exercise at the time of vaccination. Here, in separate experiments, we examined the effect of 90-minute light- to moderate-intensity cycle ergometer or outdoor walk/jog aerobic exercise performed once after immunization on serum antibody response to three different vaccines (2009 pandemic influenza H1N1, seasonal influenza, and COVID-19). Exercise took place after influenza vaccination or after the first dose of Pfizer-BioNTech COVID-19 vaccine. A mouse model of influenza A immunization was used to examine the effect of exercise on antibody response and the role of IFNα as a potential mechanism by treating mice with anti-IFNα antibody. The results show that 90 min of exercise consistently increased serum antibody to each vaccine four weeks post-immunization, and IFNα may partially contribute to the exercise-related benefit. Exercise did not increase side effects after the COVID-19 vaccination. These findings suggest that adults who exercise regularly may increase antibody response to influenza or COVID-19 vaccine by performing a single session of light- to moderate-intensity exercise post-immunization.

Exercise duration modulates upper and lower respiratory fluid cellularity, antiviral activity, and lung gene expression.

Exercise has substantial health benefits, but the effects of exercise on immune status and susceptibility to respiratory infections are less clear. Furthermore, there is limited research examining the effects of prolonged exercise on local respiratory immunity and antiviral activity. To assess the upper respiratory tract in response to exercise, we collected nasal lavage fluid (NALF) from human subjects (1) at rest, (2) after 45 min of moderate-intensity exercise, and (3) after 180 min of moderate-intensity exercise. To assess immune responses of the lower respiratory tract, we utilized a murine model to examine the effect of exercise duration on bronchoalveolar lavage (BAL) fluid immune cell content and lung gene expression. NALF cell counts did not change after 45 min of exercise, whereas 180 min significantly increased total cells and leukocytes in NALF. Importantly, fold change in NALF leukocytes correlated with the post-exercise fatigue rating in the 180-min exercise condition. The acellular portion of NALF contained strong antiviral activity against Influenza A in both resting and exercise paradigms. In mice undergoing moderate-intensity exercise, BAL total cells and neutrophils decreased in response to 45 or 90 min of exercise. In lung lobes, increased expression of heat shock proteins suggested that cellular stress occurred in response to exercise. However, a broad upregulation of inflammatory genes was not observed, even at 180 min of exercise. This work demonstrates that exercise duration differentially alters the cellularity of respiratory tract fluids, antiviral activity, and gene expression. These changes in local mucosal immunity may influence resistance to respiratory viruses, including influenza or possibly other pathogens in which nasal mucosa plays a protective role, such as rhinovirus or SARS-CoV-2.

Comparison of the Cardiovascular Benefits of Resistance, Aerobic, and Combined Exercise (CardioRACE): Rationale, design, and methods.

BACKGROUND: The benefits of aerobic exercise (AE) for cardiovascular disease (CVD) have been well documented. Resistance exercise (RE) has been traditionally examined for its effects on bone density, physical function, or metabolic health, yet few data exist regarding the benefits of RE, independent of and combined with AE, for CVD prevention. This randomized controlled trial, "Comparison of the Cardiovascular Benefits of Resistance, Aerobic, and Combined Exercise (CardioRACE)," is designed to determine the relative benefits of RE, AE, or combined RE plus AE training on CVD risk factors. METHODS: Participants are 406 inactive men and women (35-70 years) with a body mass index of 25-40 kg/m2 and blood pressure (BP) of 120-139/80-89 mm Hg without taking antihypertensive medications. Participants are randomly assigned to RE only, AE only, combined RE and AE (CE), or a no exercise control group. Participants perform supervised exercise at 50%-80% of their relative maximum intensity for both AE and RE, 3 times a week for 60 minutes per session, for 1 year (all 3 groups are time matched). RESULTS: The primary outcome is a composite z score including resting BP, low-density lipoprotein cholesterol (LDL-C), fasting glucose, and percent body fat, which is assessed at baseline, 6 months, and 12 months. Diet and outside physical activity are measured throughout the intervention for 1 year. CONCLUSION: CardioRACE (ClinicalTrials.govNCT03069092) will fill an important knowledge gap regarding the effects of RE, alone or in addition to the well-documented effects of AE. CardioRACE will help generate more comprehensive and synergistic clinical and public health strategies to prevent CVD.

STING pathway stimulation results in a differentially activated innate immune phenotype associated with low nitric oxide and enhanced antibody titers in young and aged mice.

BACKGROUND: One of the most concerning public health issues, related to vaccination and disease prevention, is the inability to induce durable immune responses following a single-dose immunization. In this regard, the nature of the inflammatory environment induced by vaccine adjuvants can negatively impact the resulting immune response. To address these concerns, new strategies to vaccine design are needed in order to improve the outcomes of immune responses, particularly in immunologically disadvantaged populations. METHODS: Comparisons of the scope of innate immune activation induced by TLR agonists versus cyclic dinucleotides (CDNs) was performed. Their effects on the activation characteristics (e.g., metabolism, cytokine secretion) of bone marrow derived dendritic cells (BMDCs) were studied. In addition, the differential effects on in vivo induction of antibody responses were measured. RESULTS: As compared to TLR ligands, the stimulation of BMDCs with CDNs induced distinctly different metabolic outcomes. Marked differences were observed in the production of nitric oxide (NO) and the cytokine BAFF. These distinct differences were correlated with improved (i.e., more rapid and persistent) vaccine antibody responses in both aged and young mice. CONCLUSIONS: Our results illustrate that the innate immune pathway targeted by adjuvants can critically impact the outcome of the immune response post-vaccination. Specifically, CDN stimulation of APCs induced an activation phenotype that was characterized by decreased innate effector molecule production (e.g., NO) and increased BAFF. This was attributed to the induction of an innate inflammatory environment that enabled the host to make the most of the existing B lymphocyte potential. The use of adjuvants that differentially engage mechanisms of innate immune activation would be particularly advantageous for the generation of robust, single dose vaccines. The results of this study demonstrated that CDNs induced differential innate activation and enhanced vaccine induced antibody responses in both young and aged mice.

Imoxin attenuates LPS-induced inflammation and MuRF1 expression in mouse skeletal muscle.

The double-stranded RNA-dependent protein kinase (PKR) contributes to inflammatory cytokine expression and disease pathogenesis in many conditions. Limited data are available on the efficacy of the PKR inhibitor imoxin to prevent lipopolysaccharide (LPS)-induced inflammation in skeletal muscle in vivo. The aim of this study was to evaluate the effect of imoxin, a PKR inhibitor, on inflammatory and atrophy signaling in skeletal muscle in response to an acute inflammatory insult with LPS. Six-week old C57BL/6J mice received vehicle (saline) or 0.5 mg/kg imoxin 24 and 2 h prior to induction of inflammation via 1 mg/kg LPS. Gastrocnemius muscles were collected 24 h post-LPS and mRNA and protein expression were assessed. LPS lead to a loss of body weight, which was similar in Imoxin+LPS. There were no differences in muscle weight among groups. LPS increased gastrocnemius mRNA expression of TNF-α and IL-1ß, and protein levels of NLRP3, all of which were attenuated by imoxin. Similarly, IL-6 mRNA and IL-1ß protein were suppressed in Imoxin+LPS compared to LPS alone. LPS increased mRNA of the atrogenes, MuRF1 and MAFbx, and imoxin attenuated the LPS-induced increase in MuRF1 mRNA, and lowered MuRF1 protein. Imoxin+LPS increased p-Akt compared to saline or LPS, whereas p-mTOR was unaltered. FoxO1 was upregulated and p-FoxO1/FoxO1 reduced by LPS, both of which were prevented by imoxin. Both LPS and Imoxin+LPS had diminished p-FoxO3/FoxO3 compared to control. These results demonstrate the potential anti-inflammatory and anti-atrophy effects of imoxin on skeletal muscle in vivo.

Is Insomnia a Risk Factor for Decreased Influenza Vaccine Response?

Healthy young adult college students (N = 133) with Insomnia (n = 65) or No Insomnia (n = 68) were compared on influenza serum antibody levels pre- and four weeks postvaccination. Volunteers underwent structured clinical interviews for sleep disorders to ensure insomnia diagnoses, as well as psychiatric interviews, physical examinations, and drug testing to ensure comorbid health problems were not potential confounds. There were significant time (both groups had increases in antibody levels pre- to postvaccination) and group (Insomnia group had lower HI antibody levels overall) main effects, but the time × group interaction was nonsignificant. Exploratory analyses did find significant PSQI x Time (p < .001) and Insomnia Status × Time (p = .002) interaction effects. Results indicate insomnia may be a risk factor for lowered immunity to the influenza virus.

Association of Sleep Quality With Cardiovascular Disease Risk and Mental Health in Law Enforcement Officers.

OBJECTIVES: The aim of the study was to determine whether sleep quality is associated with an increased risk for cardiovascular disease (CVD) or worsened mental health. METHODS: Self-reported sleep quality, 35 inflammatory factors, CVD risk factors, personal stress, police operational and organizational stress, social support, depressive symptoms, and health-related quality of life were compared among a cohort of officers. RESULTS: Of 379 officers, 39% and 27% had poor and borderline sleep quality. Sleep quality was not associated with either an altered inflammatory profile or worsened CVD risk factors. Compared with good sleepers, borderline and poor sleepers reported increased personal stress, police organizational and operational stress, and depressive symptoms, but decreased health-related quality of life. CONCLUSIONS: Poor sleep quality is prevalent in the law enforcement profession and is associated with worsened mental health but not with an increased risk for CVD.

Immune Function: Impact of Exercise and Nutritional Interventions.

This article provides a brief commentary on the accompanying article, "Nutrition and Physical Activity Interventions to Improve Immunity" by Davison, Kehaya, and Jones. The article reviews the evidence on physical exercise and/or nutrition in modulating immune response, with a specific focus on the prevention of respiratory infection. Given the large scope of the review, an overview of current findings is presented, rather than in-depth discussions, and the nutritional strategies discussed tend to focus on the strategies that have been studied in the context of exercise. Some further insight is provided in the commentary on potential mechanisms that may explain the benefits of exercise, a brief discussion on the impact of obesity and host defense, and future directions for research. In general, the article sufficiently describes the current evidence, and draws appropriate conclusions based on the evidence presented. The article is recommended for audiences that have limited background on these topics, and for those who are familiar with this line of research.

Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms.

Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise "restores" the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response.

Alkaloids and athlete immune function: caffeine, theophylline, gingerol, ephedrine, and their congeners.

Plant alkaloids are found in foods, beverages, and supplements consumed by athletes for daily nutrition, performance enhancement, and immune function improvement. This paper examined possible immunomodulatory roles of alkaloids in exercise contexts, with a focus on human studies. Four representative groups were scrutinized: (a) caffeine (guaranine, mateine); (b) theophylline and its isomers, theobromine and paraxanthine; (c) ginger alkaloids including gingerols and shogaol; and (d) ephedra alkaloids such as ephedrine and pseudoephedrine. Emerging or prospective alkaloid sources (Goji berry, Noni berry, and bloodroot) were also considered. Human in vitro and in vivo studies on alkaloids and immune function were often conflicting. Caffeine may be immunomodulatory in vivo depending on subject characteristics, exercise characteristics, and immune parameters measured. Caffeine may exhibit antioxidant capacities. Ginger may exert in vivo anti-inflammatory effects in certain populations, but it is unclear whether these effects are due to alkaloids or other biochemicals. Evidence for an immunomodulatory role of alkaloids in energy drinks, cocoa, or ephedra products in vivo is weak to nonexistent. For alkaloid sources derived from plants, variability in the reviewed studies may be due to the presence of unrecognized alkaloids or non-alkaloid compounds (which may themselves be immunomodulatory), and pre-experimental factors such as agricultural or manufacturing differences. Athletes should not look to alkaloids or alkaloid-rich sources as a means of improving immune function given their inconsistent activities, safety concerns, and lack of commercial regulation.

Vaccine technologies against avian influenza: current approaches and new directions.

The potential epidemiological human pandemic resulting from highly pathogenic avian influenza (HPAI) H5N1 has been studied extensively since the identification of the virus in the Guangdong province of China. The majority of research has focused on the unique and severe histopathological lesions induced by the virus. The severe pathological presentation of these infections has also prompted interest in identifying preventive and therapeutic approaches against HPAI. The potential severity of a HPAI pandemic and the efforts to identify effective intervention strategies have led to many novel discoveries in vaccine and antiviral development that are critically examined in this review.

The immuno-regulatory impact of orally-administered Hypericum perforatum extract on Balb/C mice inoculated with H1n1 influenza A virus.

Hypericumperforatum (H. perforatum) ethanol extract has been found to inhibit lipopolysaccharide-induced production of inflammatory mediators and cytokines in cultured macrophages. Therefore, it may be able to protect the host from excessive inflammation during viral infection. In the current study, the immune-regulatory effect of H. perforatum extract was evaluated in A549 lung epithelial cells and BALB/c mice exposed to Influenza A/PR/8/34 H1N1 virus. In A549 cells, the extract (30 µg/mL) significantly inhibited influenza virus induced monocyte chemotactic protein (MCP)-1 and interferon-γ induced protein 10 kD (IP-10), but dramatically increased interleukin-6 (IL-6). In mice inoculated intranasally with 10(7.9) EID50 of Influenza A/PR/8/34 H1N1 (high dose), daily oral treatment of H. perforatum extract at a rate of 110 mg/kg of body weight increased lung viral titer, bronchoalveolar lavage (BAL) pro-inflammatory cytokine and chemokine levels, and the infiltration of pro-inflammatory cells in the lung 5 days post-inoculation, as compared to ethanol vehicle treated mice. Transcription of suppressor of cytokine signaling 3 (SOCS3) was increased by H. perforatum extract both in A549 cells and BALB/c mice, which could have interrupted anti-viral immune response and thus led to the inefficient viral clearance and increased lung inflammation. H. perforatum treatment resulted in minor reduction in viral titer without affecting body weight when mice were inoculated with a lower dose (~10(5.0) EID50) and H. perforatum was applied in the later phase of infection. Mice challenged intranasally with high dose of influenza virus (10(7.9) EID50) suffered from a higher mortality rate when dosed with H. perforatum extract. In conclusion, the current study showed that SOCS3 elevation by H. perforatum may cause impaired immune defense against influenza virus infection and lead to higher mortality.

Enrichment of Echinacea angustifolia with Bauer alkylamide 11 and Bauer ketone 23 increased anti-inflammatory potential through interference with cox-2 enzyme activity.

Bauer alkylamide 11 and Bauer ketone 23 were previously found to be partially responsible for Echinacea angustifolia anti-inflammatory properties. This study further tested their importance using the inhibition of prostaglandin E(2) (PGE(2)) and nitric oxide (NO) production by RAW264.7 mouse macrophages in the absence and presence of lipopolysaccharide (LPS) and E. angustifolia extracts, phytochemical enriched fractions, or pure synthesized standards. Molecular targets were probed using microarray, qRT-PCR, Western blot, and enzyme assays. Fractions with these phytochemicals were more potent inhibitors of LPS-induced PGE(2) production than E. angustifolia extracts. Microarray did not detect changes in transcripts with phytochemical treatments; however, qRT-PCR showed a decrease in TNF-alpha and an increase of iNOS transcripts. LPS-induced COX-2 protein was increased by an E. angustifolia fraction containing Bauer ketone 23 and by pure phytochemical. COX-2 activity was decreased with all treatments. The phytochemical inhibition of PGE(2) production by Echinacea may be due to the direct targeting of COX-2 enzyme.

Is job-related stress the link between cardiovascular disease and the law enforcement profession?

OBJECTIVE: To determine whether job-related stress is associated with alterations in pro- and anti-atherogenic inflammatory mediators among law enforcement officers. METHODS: Markers of vascular inflammation and the self-reported stress measures of perceived stress, vital exhaustion, job strain, effort-reward imbalance, and social support were compared between officers (N = 444) and non-officers (N = 166). RESULTS: Officers had higher levels of IL-1beta, IL-6, IL-10, and TNF-alpha and lower levels of C-reactive protein and fibrinogen. No more than 4% of the variability in any of the inflammatory mediators was explained by any stress measure for either the two groups or the entire sample. CONCLUSIONS: Law enforcement officers may be at an increased risk for cardiovascular disease due to a relatively greater pro-inflammatory vascular environment. However, this increased risk cannot be attributed to either chronic stress or the work-related stress measures assessed here.

Effects of Echinacea extracts on macrophage antiviral activities.

Type I interferons are a class of cytokines synthesized by leukocytes such as macrophages that limit viral replication. We hypothesized that one mechanism whereby Echinacea spp. extracts may enhance immunity is through modulating interferon-associated macrophage pathways. We used herpes simplex viral infection in the murine macrophage cell line RAW264.7 and monitored virus-induced cell death, interferon secretion, and two intracellular proteins that indicate activation of interferon pathways. Cells were incubated with control media or extracts from four different species (E. angustifolia, E. purpurea, E. tennesseensis, E. pallida). Cells incubated with extracts prior to infection showed very modest enhancement of viability, and no increase in the secretion of interferons alpha or beta as compared to control cells. Virus-infected macrophages treated with extracts from E. purpurea showed a small (<2-fold) induction of guanylate binding protein (GBP) production, but no effect of extracts from other species was observed. In virus-infected cells, all the extracts increased the amount of inducible nitric oxide synthase (iNOS) protein, and this effect varied by type of extraction preparation. Together, these results suggest that any potential antiviral activities of Echinacea spp. extracts are likely not mediated through large inductions of Type I interferon, but may involve iNOS.